De-excitation spectroscopy of strongly interacting Rydberg gases

We present experimental results on the controlled de-excitation of Rydberg states in a cold gas of Rb atoms. The effect of the van der Waals interactions between the Rydberg atoms is clearly seen in the de-excitation spectrum and dynamics. Our observations are confirmed by numerical simulations. In particular, for off-resonant (facilitated) excitation we find that the de-excitation spectrum reflects the spatial arrangement of the atoms in the quasi one-dimensional geometry of our experiment. We discuss future applications of this technique and implications for detection and controlled dissipation schemes.Comment: 6 pages, 5 figure

The impact of chromosomal translocation locus and fusion oncogene coding sequence in synovial sarcomagenesis.

Synovial sarcomas are aggressive soft-tissue malignancies that express chromosomal translocation-generated fusion genes, SS18-SSX1 or SS18-SSX2 in most cases. Here, we report a mouse sarcoma model expressing SS18-SSX1, complementing our prior model expressing SS18-SSX2. Exome sequencing identified no recurrent secondary mutations in tumors of either genotype. Most of the few mutations identified in single tumors were present in genes that were minimally or not expressed in any of the tumors. Chromosome 6, either entirely or around the fusion gene expression locus, demonstrated a copy number gain in a majority of tumors of both genotypes. Thus, by fusion oncogene coding sequence alone, SS18-SSX1 and SS18-SSX2 can each drive comparable synovial sarcomagenesis, independent from other genetic drivers. SS18-SSX1 and SS18-SSX2 tumor transcriptomes demonstrated very few consistent differences overall. In direct tumorigenesis comparisons, SS18-SSX2 was slightly more sarcomagenic than SS18-SSX1, but equivalent in its generation of biphasic histologic features. Meta-analysis of human synovial sarcoma patient series identified two tumor-gentoype-phenotype correlations that were not modeled by the mice, namely a scarcity of male hosts and biphasic histologic features among SS18-SSX2 tumors. Re-analysis of human SS18-SSX1 and SS18-SSX2 tumor transcriptomes demonstrated very few consistent differences, but highlighted increased native SSX2 expression in SS18-SSX1 tumors. This suggests that the translocated locus may drive genotype-phenotype differences more than the coding sequence of the fusion gene created. Two possible roles for native SSX2 in synovial sarcomagenesis are explored. Thus, even specific partial failures of mouse genetic modeling can be instructive to human tumor biology

Cerebral venous sinus thrombosis

Summary: The cerebral venous system is an unusual site of thrombosis, with a particularly high incidence in young adults. This incidence has increased in past decades because of the improvement of neuroradiological techniques. Risk factors for cerebral venous sinus thrombosis overlap with those of other venous thromboembolism sites; however, some are specific for this particular anatomical district. Prognosis is favorable in most cases if diagnosis is made rapidly and treatment is promptly initiated, even if acute complications or chronic invalidity still occur in a quarter of patients. The mainstay of treatment is anticoagulation, which is necessary in order to block clot propagation and obtain recanalization. Intracranial bleeding does not contraindicate anticoagulation. Endovascular procedures are reserved for patients with a particularly severe presentation or rapidly declining neurological symptoms despite appropriate anticoagulation, although data from clinical trials are lacking. Specifically, this review addresses the epidemiology, clinical presentation and course, risk factors, and treatment of cerebral venous sinus thrombosis, with a special focus on the pediatric population

Gene targeting in the mouse nervous system

pre-printOur understanding of the development, connectivity and function of the nervous system has been facilitated by gene targeting technology. Here we summarize the historic background and the current state of this experimental approach with specific regard to neuroscience research. I. The Pioneering Experiments. Random mutagenesis is a very powerful method for elucidating gene function in simpler model organisms. Given the size of the genome and slow reproductive cycles, however, a more direct approach is required for mammalian models. This need was met in the early 1980's by establishing gene targeting in embryonic stem cells, later nicknamed mouse knockout. This technology was born at the confluence of two lines of experimentation: Firstly, the capacity of most mammalian somatic cells to carry out homologous recombination between endogenous loci and exogenous DNA was discovered. Secondly, pluripotent embryonic stem cell lines have been established that maintained the ability to intermingle with the early mouse embryo and contribute to the germline, thereby conferring heritability, even after extensive culturing in vitro

Establishment of mammalian cell lines containing multiple nonsense mutations and functional suppressor tRNA genes.

Journal ArticleWe describe the generation of mammalian cell lines carrying amber suppressor genes. Nonsense mutants in the herpes simplex virus thymidine kinase (HSV tk) gene, the Escherichia coli xanthine-guanine phosphoribosyl transferase (Eco-gpt) gene and the aminoglycoside 3' phosphotransferase gene of the Tn5 transposon (NPT-II) were isolated and characterized. Each gene was engineered with the appropriate control signals to allow expression in both E. coli and mammalian cells. Expression in E. coli made possible the use of well developed bacterial and phage genetic manipulations to isolate and characterize the nonsense mutants. Once characterized, the nonsense mutants were transferred into mammalian cells by microinjection and used, in turn, to select for amber suppressor genes. Xenopus laevis amber suppressor genes, prepared by site-specific mutagenesis of a normal X. laevis tRNA gene, were microinjected into the above cell lines and selected for the expression of one or more of the amber mutant gene products. The resulting cell lines, containing functional amber suppressor genes, are stable and exhibit normal growth rates

Isolation and characterization of Caenorhabditis elegans DNA sequences homologous to the v-abl oncogene.

Journal ArticleDNA sequences homologous to the v-abl oncogene were isolated from a Caenorhabditis elegans genomic library by their ability to hybridize with a v-src probe. The DNA sequence of 2465 nucleotides of one clone was determined. This region corresponds to the 5' protein kinase domain of v-abl plus approximately equal to 375 base pairs toward the 3' end. Four potential introns were identified. The homology between the deduced amino acid sequence of the C. elegans clone and that of the 1.2-kilobase-pair protein kinase region of v-abl is 62%. The tyrosine residue corresponding to the tyrosine that is phosphorylated in the v-src protein is conserved in the C. elegans sequence. When 95 amino acids around this tyrosine were compared with the corresponding sequences of Drosophila c-abl, v-abl, and v-src, the identities were 83%, 79%, and 56%, respectively. Hybridization of the cloned DNA with C. elegans poly(A)+ RNA revealed a major transcript of 4.4 kilobases

Hox11 paralogous genes are essential for metanephric kidney induction

Journal ArticleThe mammalian Hox complex is divided into four linkage groups containing 13 sets of paralogous genes. These paralogous genes have retained functional redundancy during evolution. For this reason, loss of only one or two Hox genes within a paralogous group often results in incompletely penetrant phenotypes which are difficult to interpret by molecular analysis. For example, mice individually mutant for Hoxa11 or Hoxd11 show no discernible kidney abnormalities. Hoxa11/Hoxd11 double mutants, however, demonstrate hypoplasia of the kidneys. As described in this study, removal of the last Hox11 paralogous member, Hoxc11, results in the complete loss of metanephric kidney induction. In these triple mutants, the metanephric blastema condenses, and expression of early patterning genes, Pax2 and Wt1, is unperturbed. Eya1 expression is also intact. Six2 expression, however, is absent, as is expression of the inducing growth factor, Gdnf. In the absence of Gdnf, ureteric bud formation is not initiated. Molecular analysis of this phenotype demonstrates that Hox11 control of early metanephric induction is accomplished by the interaction of Hox11 genes with the pax-eya-six regulatory cascade, a pathway that may be used by Hox genes more generally for the induction of multiple structures along the anteroposterior axis

Mice lacking endothelial ACE: normal blood pressure with elevated angiotensin II

Journal ArticleRecently, the concept of local renin-angiotensin systems (RAS) capable of generating angiotensin II apart from the circulation has received considerable attention. To investigate this, we generated ACE 1/3 mice in which one allele of ACE is null and the second allele was engineered to express ACE on the surface of hepatocytes. ACE 1/3 mice express no endothelial ACE and lack ACE within the lungs. Their kidneys contain <7.8% the enzyme levels present in control mice. Plasma conversion of angiotensin I to angiotensin II was 43.3% normal. The baseline blood pressure and renal function of the ACE 1/3 mice were normal, probably as a function of a marked increase of both plasma angiotensin I and angiotensin II. When exposed to 2 weeks of a salt-free diet (a stress diet stimulating the RAS), blood pressure in ACE 1/3 mice decreased to 92.3+2.0 mm Hg, a level significantly lower than that of wild-type control mice. The ACE 1/3 mice demonstrate the plasticity of the RAS and show that significant compensation is required to maintain normal, basal blood pressure in a mouse with an impaired local vascular and renal RAS. (Hypertension. 2003;41:313- 321.

A gentle introduction to multiparty asynchronous session types

This article provides a gentle introduction to multiparty session types, a class of behavioural types specifically targeted at describing protocols in distributed systems based on asynchronous communication. The type system ensures well-typed processes to enjoy non-trivial properties, including communication safety, protocol fidelity, as well as progress. The adoption of multiparty session types can positively affect the whole software lifecycle, from design to deployment, improving software reliability and reducing its development costs