Low Temperature Specific Heat of BiOX (X = Cl, Br, and I) Single Crystals

Low temperature specific heat of layered bismuth oxyhalide crystals has been studied in the temperature range from 2 to 50 K in zero and 8 T magnetic field. The expected Debye-like behaviour at the lowest temperatures (below 4-5 K) is established. Linear dependences of entropy and the Debye temperature as cross-correlation parameters are established. The small values of the Debye temperature and peculiarities of phonon spectra at lowest temperatures are discussed

Increased mRNA expression of CDKN2A is a transcriptomic marker of clinically aggressive meningiomas

Homozygous deletion of CDKN2A/B was recently incorporated into the World Health Organization classification for grade 3 meningiomas. While this marker is overall rare in meningiomas, its relationship to other CDKN2A alterations on a transcriptomic, epigenomic, and copy number level has not yet been determined. We therefore utilized multidimensional molecular data of 1577 meningioma samples from 6 independent cohorts enriched for clinically aggressive meningiomas to comprehensively interrogate the spectrum of CDKN2A alterations through DNA methylation, copy number variation, transcriptomics, and proteomics using an integrated molecular approach. Homozygous CDKN2A/B deletions were identified in only 7.1% of cases but were associated with significantly poorer outcomes compared to tumors without these deletions. Heterozygous CDKN2A/B deletions were identified in 2.6% of cases and had similarly poor outcomes as those with homozygous deletions. Among tumors with intact CDKN2A/B (without a homozygous or heterozygous deletion), we found a distinct difference in outcome based on mRNA expression of CDKN2A, with meningiomas that had elevated mRNA expression (CDKN2Ahigh) having a significantly shorter time to recurrence. The expression of CDKN2A was independently prognostic after accounting for copy number loss and consistently increased with WHO grade and more aggressive molecular and methylation groups irrespective of cohort. Despite the discordant and mutually exclusive status of the CDKN2A gene in these groups, both CDKN2Ahigh meningiomas and meningiomas with CDKN2A deletions were enriched for similar cell cycle pathways but at different checkpoints. High mRNA expression of CDKN2A was also associated with gene hypermethylation, Rb-deficiency, and lack of response to CDK inhibition. p16 immunohistochemistry could not reliably differentiate between meningiomas with and without CDKN2A deletions but appeared to correlate better with mRNA expression. These findings support the role of CDKN2A mRNA expression as a biomarker of clinically aggressive meningiomas with potential therapeutic implications

Novel regulation of Ras proteins by direct tyrosine phosphorylation and dephosphorylation

Somatic mutations in the RAS genes are frequent in human tumors, especially in pancreatic, colorectal, and non-small-cell lung cancers. Such mutations generally decrease the ability of Ras to hydrolyze GTP, maintaining the protein in a constitutively active GTP-bound form that drives uncontrolled cell proliferation. Efforts to develop drugs that target Ras oncoproteins have been unsuccessful. Recent emerging data suggest that Ras regulation is more complex than the scientific community has believed for decades. In this review, we summarize advances in the "textbook" view of Ras activation. We also discuss a novel type of Ras regulation that involves direct phosphorylation and dephosphorylation of Ras tyrosine residues. The discovery that pharmacological inhibition of the tyrosine phosphoprotein phosphatase SHP2 maintains mutant Ras in an inactive state suggests that SHP2 could be a novel drug target for the treatment of Ras-driven human cancers

LOSS OF JAK2 REGULATION VIA VHL-SOCS1 E3 UBIQUITIN HETEROCOMPLEX UNDERLIES CHUVASH POLYCYTHEMIA

Chuvash polycythemia (CP) is a rare congenital form of polycythemia caused by homozygous R200W and H191D mutations in the von Hippel-Lindau (VHL) gene whose gene product is the principal negative regulator of hypoxia-inducible factor. However, the molecular mechanisms underlying some of the hallmark features of CP such as hypersensitivity to erythropoietin are unclear. Here, we show that VHL directly binds suppressor of cytokine signalling 1 (SOCS1) to form a heterodimeric E3 ligase that targets phosphorylated (p)JAK2 for ubiquitin-mediated destruction. In contrast, CP-associated VHL mutants have altered affinity for SOCS1 and fail to engage and degrade pJAK2. Systemic administration of a highly selective JAK2 inhibitor, TG101209, reverses the disease phenotype in vhlR200W/R200W knock-in mice, a model that faithfully recapitulates human CP. These results reveal VHL as a SOCS1-cooperative negative regulator of JAK2 and provide compelling biochemical and preclinical evidence for JAK2- targeted therapy in CP patients

Raman Spectra of Bismuth Oxyhalide Single Crystals

Oxyhalogenides of bismuth BiOX (X=Cl, Br and I) are very interesting materials which find various applications as X-ray luminescent screens, anti-Stokes (frequency upshift) converters, luminophors, and photoconducting analyzers of linear polarized radiation. Since each primitive cell consist of six monoatomic sites, the structure of the reduced representation of the 15 normal modes of vibration is: Γ= $2A_{1g}(Ra.)+B_{1g}(Ra.)+ 3E_{g}(Ra.)+ 2A_{2u}(i.r.)+ 2E_{u}(i.r.)$, in which the vibrations of $A_{1g}$, $B_{1g}$ and $E_{g}$ species are active in the Raman spectrum and those of $A_{2u}$ and $E_{u}$ species are active in the infrared (i.r.) spectrum. The Raman active modes are observed in frequency range 55 - 225 $cm^{-1}$, 50 - 185 $cm^{-1 }$, and 45 - 175 $cm^{-1}$ for the BiOCl, BiOBr and BiOI single crystals respectively

SPECIFIC ISSUES OF DISTRIBUTED GENERATION IN POWER SYSTEMS

Distributed Generation Systems (DGS) gets lately more and more importance in the context of concepts re-thinking within the electricity distribution networks. Understanding the key issues of DGS such as definition, technology and integration is important for the researchers and for the workers in the field as well. This paper aims to synthesize the DGS specific issues and finally conclusions are presented