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Mediator Complex Subunit 12 (MED12) is part of the transcriptional preinitiation machinery. Mutations of its gene predominantly occur in two types of highly frequent benign tumors, uterine leiomyomas and fibroadenomas of the breast, where they apparently act as driver mutations. Nevertheless, their presence is not restricted to benign tumors having been found at considerable frequencies in uterine leiomyosarcomas, malignant phyllodes tumors, and chronic lymphocytic leukemia also. Most of the mutations are located within exon 2 of the gene but in rare cases the intron 1/exon 2 boundary or exon 1 are affected. As to their type, predominantly single nucleotide exchanges with a hotspot in one codon are found, but small deletions clustering around that hotspot also are not uncommon. These latter deletions are leaving the open reading frame intact. As to the types of mutations, so far no apparent differences between the tumor entities affected have emerged. Interestingly, this pattern with small deletions clustered around the hotspot of single nucleotide exchanges resembles that seen as a result of targeted gene editing. In contrast to other driver mutations the percentage of MED12-mutation positive tumors of independent clonal origin increases with the number of tumors per patient suggesting unknown etiological factors supporting site specific mutagenesis.  These factors may act by inducing simultaneous site-specific double strand breaks the erroneous repair of which may lead to corresponding mutations. As inducers of DNA damage and its repair such as foreign nucleic acids of the microbiome displaying sequence homology to the putative target site might play a role. Interestingly, a 16 base pair homology of the hotspot to a putative terminator base-paired hairpin sequence of a Staphylococcus aureus tRNA gene cluster has been noted which might form R-loop like structures with its target sequence thus inducing said changes.

There is no doubt that genetic factors of the host play a role in susceptibility to infectious diseases. An association between ABO blood groups and SARS-CoV-2 infection as well as the severity of COVID-19 has been suggested relatively early during the pandemic and gained enormously high public interest. It was postulated that blood group A predisposes to a higher risk of infection as well as to a much higher risk of severe respiratory disease and that people with blood group O are less frequently and less severely affected by the disease. However, as to the severity of COVID-19, a thorough summary of the existing literature does not support these assumptions in general. Accordingly, at this time, there is no reason to suppose that knowledge of a patient’s ABO phenotype should directly influence therapeutical decisions in any way. On the other hand, there are many data available supporting an association between the ABO blood groups and the risk of contracting SARS-CoV-2. To explain this association, several interactions between the virus and the host cell membrane have been proposed which will be discussed here.

Mediator Subcomplex 12 (MED12) is part of the transcriptional preinitiation machinery. Mutations of its gene predominantly occur in two types of highly frequent benign tumors, uterine leiomyomas and fibroadenomas of the breast, where they apparently act as driver mutations. Nevertheless, their presence is not restricted to benign tumors having been found at considerable frequencies in uterine leiomyosarcomas, malignant phyllodes tumors, and chronic lymphocytic leukemia also. Most of the mutations are located within exon 2 of the gene but in rare cases the intron 1/exon 2 boundary or exon 1 are affected. As to their type, predominantly single nucleotide exchanges with a hotspot in one codon are found, but small deletions clustering around that hotspot also are not uncommon. According to their presumed classification as gain-of-function mutations, these latter deletions are leaving the open reading frame intact. As to the types of mutations, so far no apparent differences between the tumor entities affected have emerged. Interestingly, this pattern with small deletions clustered around the hotspot of single nucleotide exchanges resembles that seen as a result of targeted gene editing. In contrast to other driver mutations the percentage of MED12 -mutation positive tumors of independent clonal origin increases with the number of tumors per patient suggesting unknown etiological factors supporting site specific mutagenesis.  These factors may act by inducing simultaneous site-specific double strand breaks the erroneous repair of which may lead to corresponding mutations. As inducers of DNA damage and its repair such as foreign nucleic acids of the microbiome displaying sequence homology to the putative target site might play a role. Interestingly, a 16 base pair homology of the hotspot to a putative terminator base-paired hairpin sequence of a Staphylococcus aureus tRNA gene cluster has been noted which might form R-loop like structures with its target sequence thus inducing said changes.

Our insights into the molecular pathogenesis of uterine smooth muscle tumors have improved significantly. Accordingly, in the present review, we advocate a more refined risk assessment for patients considering surgical removal of fibroids or hysterectomy, respectively, requiring morcellation. For this procedure, the risk estimates given for the iatrogenic spread of a previously unexpected malignancy considerably vary among different studies. Nearly all previous studies conducted retrospectively refer to the risk of a patient having an unexpected malignancy at the time of surgery. We feel that, more appropriately, risk should refer to the number of tumors because, as a rule, every single nodule arises independently and, thus, carries an independent risk of being malignant or not. Furthermore, whether so-called parasitic fibroids carry an underestimated risk of stepwise malignant transformation is discussed.

Chromosomal rearrangements of band 19q13.4 are frequent cytogenetic alterations in benign thyroid adenomas. Apparently, these alterations lead to the upregulation of genes encoding microRNAs of two clusters mapping to the breakpoint region, i.e. miR-371-3 and C19MC. Since members of both clusters have been associated with neoplastic growth in other tumor entities the question arises whether or not their upregulation predisposes to malignant transformation of follicular cells of the thyroid. To address this question we have quantified the expression of miR-372 and miR-520c-3p in samples of 114 thyroid cancers including eight anaplastic thyroid carcinomas, 25 follicular thyroid carcinomas, 78 papillary thyroid carcinomas (including 13 follicular variants thereof), two medullary thyroid carcinomas and one oncocytic thyroid carcinoma. Additionally, we quantified miR-371a-3p and miR-519a-3p in selected samples. While in neither of the cases miR-520c-3p and miR-519a-3p were found to be upregulated, one papillary and one anaplastic thyroid carcinoma, respectively, showed upregulation of miR-372 and miR-371a-3p. However, in these cases fluorescence in situ hybridization did not reveal rearrangements of the common breakpoint region as affected in adenomas. Thus, these rearrangements do apparently not play a major role as first steps in malignant transformation of the thyroid epithelium. Moreover, there is no evidence that 19q13.4 rearrangements characterize a subgroup of thyroid adenomas associated with a higher risk to undergo malignant transformation. Vice versa, the mechanisms by which 19q13.4 rearrangements contribute to benign tumorigenesis in the thyroid remain to be elucidated.

In this study, UV Photoluminescence (UVPL) and Differential Interference Contrast (DIC) mapping was applied for process control of a 1.2 kV 4H-SiC VDMOS fabrication process at different process stages in order to investigate the influence of shallow pits on the electrical behavior of the devices. In particular, it could be shown that UVPL and DIC mapping allows the correlation of shallow pits and the occurrence of darker regions in the UVPL images and distinguishing differently implanted regions at distinct process stages. By comparing the darker regions of the UVPL scan with the electrical blocking characteristics of the associated devices a direct correlation between the occurrence of shallow pits and the reduction of the blocking capability of the devices could be observed.

Using a combination of photoluminescence and electrical characterization, defects in the epitaxial layer of unipolar 4H-SiC power devices were matched to device characteristics and statistically analyzed. In-grown triangles had no significant effect on diode and VDMOS blocking or conduction mode, while surface triangles lead to high leakage currents even below 1 V reverse bias.

We present an extended model for the simulation of the effective minority carrier lifetime in 4H-SiC epiwafers after optical excitation. This multilayer model uses measured values (such as doping profile, point defect concentration and capture cross sections, epilayer thickness) as input parameters. The bulk lifetime and the diffusion constant are calculated from the actual time dependent excess carrier profiles, resulting in more realistic transients having different decay regimes than in other models. This enables a better understanding of optical lifetime measurements.

The development of bipolar 4H-SiC devices for high blocking voltages requires the growth of high carrier lifetime epitaxial layers with low Z1/2 concentrations. This paper shows a comprehensive investigation of the influence of epitaxial growth parameters (C/Si ratio and growth temperature) on Z1/2 concentration and minority carrier lifetime. On the basis of a discovered exponential correlation of Z1/2 with the C/Si ratio and growth temperature, a competitive low Z1/2 concentration of 1.9∙1012 cm-3 could be achieved by lowering the growth temperature and switching to higher C/Si ratio. Thermodynamic considerations by an Arrhenius approach reveal a dependency of the formation enthalpy of Z1/2 on the thermal process and process conditions of the epitaxial growth. Furthermore, the correlation between Z1/2 and the effective minority carrier lifetime confirms the occurrence of a necessary second recombination mechanism beside the common recombination at deep levels by Shockley-Read-Hall for low Z1/2 concentration.

Carrier lifetime measurements and wafer mappings have been done on several different 4H SiC epiwafers to compare two different measurement techniques, time-resolved photoluminescence and microwave induced photoconductivity decay. The absolute values of the decay time differ by a factor of two, as expected from recombination and measurement theory. Variations within each wafer are comparable with the two techniques. Both techniques are shown to be sensitive to substrate quality and distribution of extended defects.