The area of horizons and the trapped region

This paper considers some fundamental questions concerning marginally trapped surfaces, or apparent horizons, in Cauchy data sets for the Einstein equation. An area estimate for outermost marginally trapped surfaces is proved. The proof makes use of an existence result for marginal surfaces, in the presence of barriers, curvature estimates, together with a novel surgery construction for marginal surfaces. These results are applied to characterize the boundary of the trapped region.Comment: 44 pages, v3: small changes in presentatio

Unconstrained mining of transcript data reveals increased alternative splicing complexity in the human transcriptome

Mining massive amounts of transcript data for alternative splicing information is paramount to help understand how the maturation of RNA regulates gene expression. We developed an algorithm to cluster transcript data to annotated genes to detect unannotated splice variants. A higher number of alternatively spliced genes and isoforms were found compared to other alternative splicing databases. Comparison of human and mouse data revealed a marked increase, in human, of splice variants incorporating novel exons and retained introns. Previously unannotated exons were validated by tiling array expression data and shown to correspond preferentially to novel first exons. Retained introns were validated by tiling array and deep sequencing data. The majority of retained introns were shorter than 500 nt and had weak polypyrimidine tracts. A subset of retained introns matching small RNAs and displaying a high GC content suggests a possible coordination between splicing regulation and production of noncoding RNAs. Conservation of unannotated exons and retained introns was higher in horse, dog and cow than in rodents, and 64% of exon sequences were only found in primates. This analysis highlights previously bypassed alternative splice variants, which may be crucial to deciphering more complex pathways of gene regulation in human.info:eu-repo/semantics/publishedVersio

Evaluation of Methodologies for Microrna Biomarker Detection by Next Generation Sequencing

In recent years, microRNAs (miRNAs) in tissues and biofluids have emerged as a new class of promising biomarkers for numerous diseases. Blood-based biomarkers are particularly desirable since serum or plasma is easily accessible and can be sampled repeatedly. To comprehensively explore the biomarker potential of miRNAs, sensitive, accurate and cost-efficient miRNA profiling techniques are required. Next generation sequencing (NGS) is emerging as the preferred method for miRNA profiling; offering high sensitivity, single-nucleotide resolution and the possibility to profile a considerable number of samples in parallel. Despite the excitement about miRNA biomarkers, challenges associated with insufficient characterization of the sequencing library preparation efficacy, precision and method-related quantification bias have not been addressed in detail and are generally underappreciated in the wider research community. Here, we have tested in parallel four commercially available small RNA sequencing kits against a cohort of samples comprised of human plasma, human serum, murine brain tissue and a reference library containing ~ 950 synthetic miRNAs. We discuss the advantages and limits of these methodologies for massive parallel microRNAs profiling. This work can serve as guideline for choosing an adequate library preparation method, based on sensitivity, specificity and accuracy of miRNA quantification, workflow convenience and potential for automation

Generalized inverse mean curvature flows in spacetime

Motivated by the conjectured Penrose inequality and by the work of Hawking, Geroch, Huisken and Ilmanen in the null and the Riemannian case, we examine necessary conditions on flows of two-surfaces in spacetime under which the Hawking quasilocal mass is monotone. We focus on a subclass of such flows which we call uniformly expanding, which can be considered for null as well as for spacelike directions. In the null case, local existence of the flow is guaranteed. In the spacelike case, the uniformly expanding condition leaves a 1-parameter freedom, but for the whole family, the embedding functions satisfy a forward-backward parabolic system for which local existence does not hold in general. Nevertheless, we have obtained a generalization of the weak (distributional) formulation of this class of flows, generalizing the corresponding step of Huisken and Ilmanen's proof of the Riemannian Penrose inequality.Comment: 21 pages, 1 figur

Apparent wave function collapse caused by scattering

Some experimental implications of the recent progress on wave function collapse are calculated. Exact results are derived for the center-of-mass wave function collapse caused by random scatterings and applied to a range of specific examples. The results show that recently proposed experiments to measure the GRW effect are likely to fail, since the effect of naturally occurring scatterings is of the same form as the GRW effect but generally much stronger. The same goes for attempts to measure the collapse caused by quantum gravity as suggested by Hawking and others. The results also indicate that macroscopic systems tend to be found in states with (Delta-x)(Delta-p) = hbar/sqrt(2), but microscopic systems in highly tiltedly squeezed states with (Delta-x)(Delta-p) >> hbar.Comment: Final published version. 20 pages, Plain TeX, no figures. Online at http://astro.berkeley.edu/~max/collapse.html (faster from the US), from http://www.mpa-garching.mpg.de/~max/collapse.html (faster from Europe) or from [email protected]

Primary growth hormone insensitivity (Laron syndrome) and acquired hypothyroidism: a case report

<p>Abstract</p> <p>Introduction</p> <p>Primary growth hormone resistance or growth hormone insensitivity syndrome, also known as Laron syndrome, is a hereditary disease caused by deletions or different types of mutations in the growth hormone receptor gene or by post-receptor defects. This disorder is characterized by a clinical appearance of severe growth hormone deficiency with high levels of circulating growth hormone in contrast to low serum insulin-like growth factor 1 values.</p> <p>Case presentation</p> <p>We report the case of a 15-year-old Caucasian girl who was diagnosed with Silver-Russell syndrome at the age of four and a half years. Recombinant growth hormone was administered for 18 months without an appropriate increase in growth velocity. At the age of seven years, her serum growth hormone levels were high, and an insulin-like growth factor 1 generation test did not increase insulin-like growth factor 1 levels (baseline insulin-like growth factor 1 levels, 52 μg/L; reference range, 75 μg/L to 365 μg/L; and peak, 76 μg/L and 50 μg/L after 12 and 84 hours, respectively, from baseline). The genetic analysis showed that the patient was homozygous for the R217X mutation in the growth hormone receptor gene, which is characteristic of Laron syndrome. On the basis of these results, the diagnosis of primary growth hormone insensitivity syndrome was made, and recombinant insulin-like growth factor 1 therapy was initiated. The patient's treatment was well tolerated, but unexplained central hypothyroidism occurred at the age of 12.9 years. At the age of 15 years, when the patient's sexual development was almost completed and her menstrual cycle occurred irregularly, her height was 129.8 cm, which is 4.71 standard deviations below the median for normal girls her age.</p> <p>Conclusion</p> <p>The most important functional tests for the diagnosis of growth hormone insensitivity are the insulin-like growth factor 1 generation test and genetic analysis. Currently, the only effective treatment is daily administration of recombinant insulin-like growth factor 1 starting from early childhood. However, these patients show a dramatically impaired final height. In our case, unexplained central hypothyroidism occurred during treatment.</p

Does the universe in fact contain almost no information?

At first sight, an accurate description of the state of the universe appears to require a mind-bogglingly large and perhaps even infinite amount of information, even if we restrict our attention to a small subsystem such as a rabbit. In this paper, it is suggested that most of this information is merely apparent, as seen from our subjective viewpoints, and that the algorithmic information content of the universe as a whole is close to zero. It is argued that if the Schr\"odinger equation is universally valid, then decoherence together with the standard chaotic behavior of certain non-linear systems will make the universe appear extremely complex to any self-aware subsets that happen to inhabit it now, even if it was in a quite simple state shortly after the big bang. For instance, gravitational instability would amplify the microscopic primordial density fluctuations that are required by the Heisenberg uncertainty principle into quite macroscopic inhomogeneities, forcing the current wavefunction of the universe to contain such Byzantine superpositions as our planet being in many macroscopically different places at once. Since decoherence bars us from experiencing more than one macroscopic reality, we would see seemingly complex constellations of stars etc, even if the initial wavefunction of the universe was perfectly homogeneous and isotropic.Comment: 17 pages, LATeX, no figures. Online with refs at http://astro.berkeley.edu/~max/nihilo.html (faster from the US), from http://www.mpa-garching.mpg.de/~max/nihilo.html (faster from Europe) or from [email protected]

Towards the Physical Map of the Trypanosoma cruzi Nuclear Genome: Construction of YAC and BAC Libraries of the Reference Clone T. cruzi CL-Brener

Strategies to construct the physical map of the Trypanosoma cruzi nuclear genome have to capitalize on three main advantages of the parasite genome, namely (a) its small size, (b) the fact that all chromosomes can be defined, and many of them can be isolated by pulse field gel electrophoresis, and (c) the fact that simple Southern blots of electrophoretic karyotypes can be used to map sequence tagged sites and expressed sequence tags to chromosomal bands. A major drawback to cope with is the complexity of T. cruzi genetics, that hinders the construction of a comprehensive genetic map. As a first step towards physical mapping, we report the construction and partial characterization of a T. cruzi CL-Brener genomic library in yeast artificial chromosomes (YACs) that consists of 2,770 individual YACs with a mean insert size of 365 kb encompassing around 10 genomic equivalents. Two libraries in bacterial artificial chromosomes (BACs) have been constructed, BACI and BACII. Both libraries represent about three genome equivalents. A third BAC library (BAC III) is being constructed. YACs and BACs are invaluable tools for physical mapping. More generally, they have to be considered as a common resource for research in Chagas diseaseInstituto de Investigaciones en Ingeniería Genética y Biología MolecularEscola Paulista de MedicinaCBMUniversidade de São PauloUniversidade Federal do Rio de JaneiroIPBUniversidad Central de VenezuelaUSBInstituto Oswaldo CruzCEPHUNIFESP, EPMSciEL