A baseline for the genetic stock identification of Atlantic herring, Clupea harengus, in ICES Divisions 6.a, 7.b-c

Atlantic herring in International Council for Exploration of the Sea (ICES) Divisions 6.a, 7.b-c comprises at least three populations, distinguished by temporal and spatial differences in spawning, which have until recently been managed as two stocks defined by geographical delineators. Outside of spawning the populations form mixed aggregations, which are the subject of acoustic surveys. The inability to distinguish the populations has prevented the development of separate survey indices and separate stock assessments. A panel of 45 single-nucleotide polymorphisms, derived from whole-genome sequencing, were used to genotype 3480 baseline spawning samples (2014-2021). A temporally stable baseline comprising 2316 herring from populations known to inhabit Division 6.a was used to develop a genetic assignment method, with a self-assignment accuracy greater than 90%. The long-term temporal stability of the assignment model was validated by assigning archive (2003-2004) baseline samples (270 individuals) with a high level of accuracy. Assignment of non-baseline samples (1514 individuals) from Divisions 6.a, 7.b-c indicated previously unrecognized levels of mixing of populations outside of the spawning season. The genetic markers and assignment models presented constitute a 'toolbox' that can be used for the assignment of herring caught in mixed survey and commercial catches in Division 6.a into their population of origin with a high level of accuracy

A baseline for the genetic stock identification of Atlantic herring, Clupea harengus, in ICES Divisions 6.a, 7.b-c

Atlantic herring in International Council for Exploration of the Sea (ICES) Divisions 6.a, 7.b-c comprises at least three populations, distinguished by temporal and spatial differences in spawning, which have until recently been managed as two stocks defined by geographical delineators. Outside of spawning the populations form mixed aggregations, which are the subject of acoustic surveys. The inability to distinguish the populations has prevented the development of separate survey indices and separate stock assessments. A panel of 45 single-nucleotide polymorphisms, derived from whole-genome sequencing, were used to genotype 3480 baseline spawning samples (2014-2021). A temporally stable baseline comprising 2316 herring from populations known to inhabit Division 6.a was used to develop a genetic assignment method, with a self-assignment accuracy greater than 90%. The long-term temporal stability of the assignment model was validated by assigning archive (2003-2004) baseline samples (270 individuals) with a high level of accuracy. Assignment of non-baseline samples (1514 individuals) from Divisions 6.a, 7.b-c indicated previously unrecognized levels of mixing of populations outside of the spawning season. The genetic markers and assignment models presented constitute a 'toolbox' that can be used for the assignment of herring caught in mixed survey and commercial catches in Division 6.a into their population of origin with a high level of accuracy

An epigenomic approach to therapy for tamoxifen-resistant breast cancer

Tamoxifen has been a frontline treatment for estrogen receptor alpha (ERα)-positive breast tumors in premenopausal women. However, resistance to tamoxifen occurs in many patients. ER still plays a critical role in the growth of breast cancer cells with acquired tamoxifen resistance, suggesting that ERα remains a valid target for treatment of tamoxifen-resistant (Tam-R) breast cancer. In an effort to identify novel regulators of ERα signaling, through a small-scale siRNA screen against histone methyl modifiers, we found WHSC1, a histone H3K36 methyltransferase, as a positive regulator of ERα signaling in breast cancer cells. We demonstrated that WHSC1 is recruited to the ERα gene by the BET protein BRD3/4, and facilitates ERα gene expression. The small-molecule BET protein inhibitor JQ1 potently suppressed the classic ERα signaling pathway and the growth of Tam-R breast cancer cells in culture. Using a Tam-R breast cancer xenograft mouse model, we demonstrated in vivo anti-breast cancer activity by JQ1 and a strong long-lasting effect of combination therapy with JQ1 and the ER degrader fulvestrant. Taken together, we provide evidence that the epigenomic proteins BRD3/4 and WHSC1 are essential regulators of estrogen receptor signaling and are novel therapeutic targets for treatment of Tam-R breast cancer

Longevity Improvement of Optically Activated, High Gain GaAs Photoconductive Semiconductor Switches

The longevity of high gain GaAs photoconductive semiconductor switches (PCSS) has been extended to over 100 million pulses at 23A, and over 100 pulses at 1kA. This is achieved by improving the ohmic contacts by doping the semi-insulating GaAs underneath the metal, and by achieving a more uniform distribution of contact wear across the entire switch by distributing the trigger light to form multiple filaments. This paper will compare various approaches to doping the contacts, including ion implantation, thermal diffusion, and epitaxial growth. The device characterization also includes examination of the filament behavior using open-shutter, infra-red imaging during high gain switching. These techniques provide information on the filament carrier densities as well as the influence that the different contact structures and trigger light distributions have on the distribution of the current in the devices. This information is guiding the continuing refinement of contact structures and geometries for further improvements in switch longevity

Longevity improvement of optically activated, high gain GaAs photoconductive semiconductor switches

The longevity of high gain GaAs photoconductive semiconductor switches (PCSS) has been extended to over 100 million pulses at 23A, and over 100 pulses at 1kA. This is achieved by improving the ohmic contacts by doping the semi-insulating GaAs underneath the metal, and by achieving a more uniform distribution of contact wear across the entire switch by distributing the trigger light to form multiple filaments. This paper will compare various approaches to doping the contacts, including ion implantation, thermal diffusion, and epitaxial growth. The device characterization also includes examination of the filament behavior using open-shutter, infra-red imaging during high gain switching. These techniques provide information on the filament carrier densities as well as the influence that the different contact structures and trigger light distributions have on the distribution of the current in the devices. This information is guiding the continuing refinement of contact structures and geometries for further improvements in switch longevity

Relationship between Tumor DNA Methylation Status and Patient Characteristics in African-American and European-American Women with Breast Cancer

Aberrant DNA methylation is critical for development and progression of breast cancer. We investigated the association of CpG island methylation in candidate genes and clinicopathological features in 65 African-American (AA) and European-American (EA) breast cancer patients. Quantitative methylation analysis was carried out on bisulfite modified genomic DNA and sequencing (pyrosequencing) for promoter CpG islands of p16, ESR1, RASSF1A, RARβ2, CDH13, HIN1, SFRP1 genes and the LINE1 repetitive element using matched paired non-cancerous and breast tumor specimen (32 AA and 33 EA women). Five of the genes, all known tumor suppressor genes (RASSF1A, RARβ2, CDH13, HIN1 and SFRP1), were found to be frequently hypermethylated in breast tumor tissues but not in the adjacent non-cancerous tissues. Significant differences in the CDH13 methylation status were observed by comparing DNA methylation between AA and EA patients, with more obvious CDH13 methylation differences between the two patient groups in the ER- disease and among young patients (age<50). In addition, we observed associations between CDH13, SFRP1, and RASSF1A methylation and breast cancer subtypes and between SFRP1 methylation and patient's age. Furthermore, tumors that received neoadjuvant therapy tended to have reduced RASSF1A methylation when compared with chemotherapy naïve tumors. Finally, Kaplan Meier survival analysis showed a significant association between methylation at 3 loci (RASSF1A, RARβ2 and CDH13) and reduced overall disease survival. In conclusion, the DNA methylation status of breast tumors was found to be significantly associated with clinicopathological features and race/ethnicity of the patients

Selected sociodemographic factors and related differences in patterns of alcohol use among university students in Slovakia

Background: Alcohol use and misuse and their relation to sociodemograhic factors are well studied among university students in Western European countries and the USA, but less is known about students in Eastern Europe. The historical past as communistic countries might have affected the social life among these populations, which is again one of the main factors determining the alcohol consumption among university students. The aim of our study was to assess the association of selected sociodemographic factors with different patterns of alcohol use among university students in Slovakia. Methods: A sample of 813 young adults (mean age 21.1 years, 63.8% females; response rate of 71%) from four universities in Kosice answered questions about their sociodemographic background and about alcohol use. To obtain a detailed picture of different aspects, alcohol use was measured by four variables: frequency of alcohol use, heavy episodic drinking, frequency of drunkenness and problem drinking. Four separate logistic regression models were used to assess the association between sociodemographic and alcohol-related variables. To assess the potentially different effects in both genders, all two-way interactions with gender were tested. Results: While 41% of the students drank alcohol once a week or more often, 77% reported heavy episodic drinking and 49% had been drunk more than once in the last month. Problem drinking existed in 23.3% of the sample. Gender was consistently associated with all four alcohol-related variables, with males being at higher risk. A higher study year was associated only with lower levels of heavy episodic drinking, but displayed no association with the other studied variables. Living with parents during the semester was consistently associated with less frequent heavy episodic drinking, drunkenness episodes, and problem drinking while having an intimate relationship was associated with less problem drinking only. Conclusions: Our findings for the university students from Slovakia are in line with previous studies in Western Europe. Additionally, it appears that frequent alcohol use, excessive alcohol use (heavy episodic drinking and drunkenness) and problem drinking among university students represent a continuum and are influenced by the same sociodemographic factors