Distribution of particles which produces a "smart" material

If $A_q(\beta, \alpha, k)$ is the scattering amplitude, corresponding to a potential $q\in L^2(D)$, where $D\subset\R^3$ is a bounded domain, and $e^{ik\alpha \cdot x}$ is the incident plane wave, then we call the radiation pattern the function $A(\beta):=A_q(\beta, \alpha, k)$, where the unit vector $\alpha$, the incident direction, is fixed, and $k>0$, the wavenumber, is fixed. It is shown that any function $f(\beta)\in L^2(S^2)$, where $S^2$ is the unit sphere in $\R^3$, can be approximated with any desired accuracy by a radiation pattern: $||f(\beta)-A(\beta)||_{L^2(S^2)}<\epsilon$, where $\epsilon>0$ is an arbitrary small fixed number. The potential $q$, corresponding to $A(\beta)$, depends on $f$ and $\epsilon$, and can be calculated analytically. There is a one-to-one correspondence between the above potential and the density of the number of small acoustically soft particles $D_m\subset D$, $1\leq m\leq M$, distributed in an a priori given bounded domain $D\subset\R^3$. The geometrical shape of a small particle $D_m$ is arbitrary, the boundary $S_m$ of $D_m$ is Lipschitz uniformly with respect to $m$. The wave number $k$ and the direction $\alpha$ of the incident upon $D$ plane wave are fixed.It is shown that a suitable distribution of the above particles in $D$ can produce the scattering amplitude $A(\alpha',\alpha)$, $\alpha',\alpha\in S^2$, at a fixed $k>0$, arbitrarily close in the norm of $L^2(S^2\times S^2)$ to an arbitrary given scattering amplitude $f(\alpha',\alpha)$, corresponding to a real-valued potential $q\in L^2(D)$.Comment: corrected typo

HSF2BP negatively regulates homologous recombination in DNA interstrand crosslink repair

The tumor suppressor BRCA2 is essential for homologous recombination (HR), replication fork stability and DNA interstrand crosslink (ICL) repair in vertebrates. We show that ectopic production of HSF2BP, a BRCA2-interacting protein required for meiotic HR during mouse spermatogenesis, in non-germline human cells acutely sensitize them to ICL-inducing agents (mitomycin C and cisplatin) and PARP inhibitors, resulting in a phenotype characteristic of cells from Fanconi anemia (FA) patients. We biochemically recapitulate the suppression of ICL repair and establish that excess HSF2BP compromises HR by triggering the removal of BRCA2 from the ICL site and thereby preventing the loading of RAD51. This establishes ectopic expression of a wild-type meiotic protein in the absence of any other protein-coding mutations as a new mechanism that can lead to an FA-like cellular phenotype. Naturally occurring elevated production of HSF2BP in tumors may be a source of cancer-promoting genomic instability and also a targetable vulnerability

Proper genomic profiling of (BRCA1-mutated) basal-like breast carcinomas requires prior removal of tumor infiltrating lymphocytes

BRCA1-mutated breast carcinomas may have distinct biological features, suggesting the involvement of specific oncogenic pathways in tumor development. The identification of genomic aberrations characteristic for BRCA1-mutated breast carcinomas could lead to a better understanding of BRCA1-associated oncogenic events and could prove valuable in clinical testing for BRCA1-involvement in patients. Methods: For this purpose, genomic and gene expression profiles of basal-like BRCA1-mutated breast tumors (n=27) were compared with basal-like familial BRCAX (non-. BRCA1/. 2/. CHEK2*1100delC) tumors (n=14) in a familial cohort of 120 breast carcinomas. Results: Genome wide copy number profiles of the BRCA1-mutated breast carcinomas in our data appeared heterogeneous. Gene expression analyses identifi

ELOF1 is a transcription-coupled DNA repair factor that directs RNA polymerase II ubiquitylation

Two side-by-side papers report that the transcription elongation factor ELOF1 drives transcription-coupled repair and prevents replication stress.Cells employ transcription-coupled repair (TCR) to eliminate transcription-blocking DNA lesions. DNA damage-induced binding of the TCR-specific repair factor CSB to RNA polymerase II (RNAPII) triggers RNAPII ubiquitylation of a single lysine (K1268) by the CRL4(CSA) ubiquitin ligase. How CRL4(CSA) is specifically directed towards K1268 is unknown. Here, we identify ELOF1 as the missing link that facilitates RNAPII ubiquitylation, a key signal for the assembly of downstream repair factors. This function requires its constitutive interaction with RNAPII close to K1268, revealing ELOF1 as a specificity factor that binds and positions CRL4(CSA) for optimal RNAPII ubiquitylation. Drug-genetic interaction screening also revealed a CSB-independent pathway in which ELOF1 prevents R-loops in active genes and protects cells against DNA replication stress. Our study offers key insights into the molecular mechanisms of TCR and provides a genetic framework of the interplay between transcriptional stress responses and DNA replication.Cancer Signaling networks and Molecular Therapeutic

Huntingtin with an expanded polyglutamine repeat affects the Jab1-p27(Kip1) pathway

Neurological Motor Disorder