Immune Checkpoint Blockade in Advanced Cutaneous Squamous Cell Carcinoma: What Do We Currently Know in 2020?

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer that predominantly arises in chronically sun-damaged skin. Immunosuppression, genetic disorders such as xeroderma pigmentosum (XP), exposure to certain drugs and environmental noxae have been identified as major risk factors. Surgical removal of cSCC is the therapy of choice and mostly curative in early stages. However, a minority of patients develop locally advanced tumors or distant metastases that are still challenging to treat. Immune checkpoint blockade (ICB) targeting CTLA-4, PD-L1 and PD-1 has tremendously changed the field of oncological therapy and especially the treatment of skin cancers as tumors with a high mutational burden. In this review, we focus on the differences between cSCC and cutaneous melanoma (CM) and their implications on therapy, summarize the current evidence on ICB for the treatment of advanced cSCC and discuss the chances and pitfalls of this therapy option for this cancer entity. Furthermore, we focus on special subgroups of interest such as organ transplant recipients, patients with hematologic malignancies, XP and field cancerization.     

A non-conserved sequence in the 5'region of the CYH2 intron from Saccharomyces cerevisiae controls splicing efficiency of the pre-mRNA

The CYH2 gene from Saccharomyces cerevisiae containing one 510 bp intron is spliced inefficiently. We have shown previously that a non-conserved sequence within the intron is responsible for this low splicing efficiency. Using synthetic oligonucleotides comprising the identified region we show in this report that a very short region contains the specificity to act negatively on the splicing efficiency of the CYH2 gene. Furthermore, this sequence influences the splicing efficiency only when it is placed close to the 5' splice site of the gene. Investigations with chimeric CYH2/beta-actin genes show that this sequence acts independent from its natural surroundings. We propose that this sequence might interact with splicing factor(s).     

Characterization of activated sludge flocs by confocal laser scanning microscopy and image analysis

In this study we present a new approach to determine volumes, heterogeneity factors, and compositions of the bacterial population of activated sludge flocs by 3D confocal imaging. After staining the fresh flocs with fluorescein-isothiocyanate, 75 stacks of images (containing approx. 3000 flocs) were acquired with a confocal laser scanning microscope. The self-developed macro 3D volume and surface determination for the KS 400 software package combined the images of one stack to a 3D image and calculated the real floc volume and surface. We determined heterogeneity factors like the ratio of real floc surface to the surface of a sphere with the respective volume and the fractal dimension (D(f)). According to their significant influence on floc integrity and quality, we also investigated the chemical composition of flocs and quantified their bacterial population structure by using group-specific rRNA-targeted probes for fluorescence in situ hybridization. By a settling experiment we enriched flocs with poor settling properties and determined the above-mentioned parameters. This approach revealed shifts in floc volume, heterogeneity, and bacterial and chemical composition according to the settling quality of the flocs.     

Influence of personality on travel-related consumer-generated media creation

While a growing number of travelers engages in consumer-generated media (CGM) use and creation, the gap between the number of users and the number of actual content creators remains large. It is important to find out what drives this minority of creators and what makes them different from those who only use CGM. Personality has been found to be a particularly influential trait that predicts behavior. The influence of personality on travel CGM creation was investigated and the results indicate that travelers’ personality traits significantly influence perceived barriers to content creation, motivations to engage in CGM creation, and specific creation behaviors. Contributions and implications are discussed from both a theoretical and a practical perspective.     

Unequal representation of women and men in energy company boards and management groups: Are there implications for mitigation?

This survey shows that female representation in boards and management groups of large energy companies in Germany, Spain and Sweden is far from being gender-equal. Of the 464 companies surveyed, 295 (64%) had no women at all in boards or management groups and only 5% could be considered gender-equal by having 40% or more women in such positions. Interviews with energy companies confirmed current trends that gender equality efforts within decision-making in business are weak or non-existent. The findings are discussed against the background of differences in risk perceptions among women and men, evidence of women’s impact on boards and companies’ performance and the substantial risks related to unabated climate change. Research is suggested for exploring potential impacts on energy companies' performance with more women in the boards when it comes to mitigation activities.     

Alanine : glyoxylate aminotransferase of Saccharomyces cerevisiae-encoding gene AGX1 and metabolic significance

Alanine : glyoxylate aminotransferase is one of three different enzymes used for glycine synthesis in Saccharomyces cerevisiae. The open reading frame YFL030w (named AGX1 in the following), encoding this enzyme, was identified by comparing enzyme specific activities in knockout strains. While 100% activity was detectable in the parental strain, 2% was found in a YFL030w::kanMX4 strain. The ORF found at that locus was suspected to encode alanine : glyoxylate aminotransferase because its predicted amino acid sequence showed 23% identity to the human homologue. Since the YFL030w::kanMX4 strain showed no glycine auxtrophic phenotype, AGX1 was replaced by KanMX4 in a Delta GLY1 Delta SHM1 Delta SHM2 background. These background mutations, which cause inactivation of threonine aldolase, mitochondrial and cytosolic serine hydroxymethyltransferase, respectively, lead to a conditional glycine auxotrophy. This means that growth is not possible on glucose but on ethanol as the sole carbon source. Additional disruption of AGX1 revealed a complete glycine auxotrophy. Complementation was observed by transformation with a plasmid-encoded AGX1.     

The structural efficiency of orthotropic stalks,stems and tubes

An optimised structure is one which uses the smallest quantity of the best material to perform its function, with adequate safety factor or margin for error. Structural optimisation occurs not only in mechanical engineering, but also in nature: plants with hollow stems or stalks gain a height advantage, and are thus more efficient, by approaching the optimum shape. Here we consider the optimisation of orthotropic tubes, typifying, in a mechanical sense, stalk and stem. The stiffness and strength of orthotropic tubes of initially circular section are reviewed, and diagrams are proposed which allow the optimum section shape to be selected.     

The significance of air velocity and turbulence intensity for responses to horizontal drafts in a constant air temperature of 23°C

Aim: The aim was to prove the significance of air velocity and turbulence intensity on the responses to drafts and if air velocity is adequately weighted in the draft rating model (DR-model) proposed in ISO 7730 (1994). Methods: Seventeen healthy persons (9 women, 8 men, 19–51 yr) took part in 12 randomly arranged 1-h sessions where horizontal drafts were directed towards the dorsolateral body sites of the sedentary persons. Mean air velocity was varied in 4 (  m/s) and turbulence intensity in 3 steps (Tu: <30,≈50,>70%) but were kept constant during the single sessions, whereas air velocities were increased every 15 min in the basic experiments performed for the DR-model. Air temperature was 23°C, humidity varied between 40% and 60%. Subjective perception and annoyance due to drafts were registered every 5 min using a list of prescribed body parts and skin temperature was measured continuously throughout the sessions at the forearm and at the neck. Results: Draft-induced general annoyance (if draft-induced annoyance was stated for at least one body site) and draft-induced local annoyance as stated for the neck and for the forearm increased with air velocity and/or with turbulence intensity. The decrease in skin temperature, however, was only related to air velocity but not to turbulence intensity. Air velocities are obviously not accurately weighted in the draft-rating model (ISO 7730, 1994). As compared to the effects observed here, the effects predicted with the DR-model were smaller in case of mean air velocities of 0.3 m/s and less but greater for 0.4 m/s. Concerning rather sedentary persons it seems that drafts are tolerable as long as mean air velocities do not exceed 0.2 m/s and as long as turbulence intensity remains below 30% in air temperature of 23°C.

Relevance to industry

Drafts are the most annoying climatic factor at many workplaces and assumed to reduce satisfaction with work, to impair performance and perhaps even health (Griefahn et al., Ind. Health 38 (2000b) 30). The limitation of drafts is therefore an important contribution to industrial safety. Using the draft-rating model proposed in ISO 7730 (1994) for the evaluation and for the prediction of draft-induced annoyance, it must be considered that the model underestimates the effects of drafts in case of air velocities of 0.3 m/s which prevail at more than 85% of workplaces in offices and in the industry (Griefahn, 1999; Zhou, Ph.D. Thesis, International Center for Indoor Environment and Energy, Department of Energy Engineering, Technical University of Denmark, Lyngby, 1999).