263 research outputs found
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]
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]
Identifying Alternative Hyper-Splicing Signatures in MG-Thymoma by Exon Arrays
BACKGROUND: The vast majority of human genes (>70%) are alternatively spliced. Although alternative pre-mRNA processing is modified in multiple tumors, alternative hyper-splicing signatures specific to particular tumor types are still lacking. Here, we report the use of Affymetrix Human Exon Arrays to spot hyper-splicing events characteristic of myasthenia gravis (MG)-thymoma, thymic tumors which develop in patients with MG and discriminate them from colon cancer changes. METHODOLOGY/PRINCIPAL FINDINGS: We combined GO term to parent threshold-based and threshold-independent ad-hoc functional statistics with in-depth analysis of key modified transcripts to highlight various exon-specific changes. These denote alternative splicing in MG-thymoma tumors compared to healthy human thymus and to in-house and Affymetrix datasets from colon cancer and healthy tissues. By using both global and specific, term-to-parent Gene Ontology (GO) statistical comparisons, our functional integrative ad-hoc method allowed the detection of disease-relevant splicing events. CONCLUSIONS/SIGNIFICANCE: Hyper-spliced transcripts spanned several categories, including the tumorogenic ERBB4 tyrosine kinase receptor and the connective tissue growth factor CTGF, as well as the immune function-related histocompatibility gene HLA-DRB1 and interleukin (IL)19, two muscle-specific collagens and one myosin heavy chain gene; intriguingly, a putative new exon was discovered in the MG-involved acetylcholinesterase ACHE gene. Corresponding changes in spliceosome composition were indicated by co-decreases in the splicing factors ASF/SF(2) and SC35. Parallel tumor-associated changes occurred in colon cancer as well, but the majority of the apparent hyper-splicing events were particular to MG-thymoma and could be validated by Fluorescent In-Situ Hybridization (FISH), Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and mass spectrometry (MS) followed by peptide sequencing. Our findings demonstrate a particular alternative hyper-splicing signature for transcripts over-expressed in MG-thymoma, supporting the hypothesis that alternative hyper-splicing contributes to shaping the biological functions of these and other specialized tumors and opening new venues for the development of diagnosis and treatment approaches
Enhancement of Cell Membrane Invaginations, Vesiculation and Uptake of Macromolecules by Protonation of the Cell Surface
The different pathways of endocytosis share an initial step involving local inward curvature of the cell’s lipid bilayer. It has been shown that to generate membrane curvature, proteins or lipids enforce transversal asymmetry of the plasma membrane. Thus it emerges as a general phenomenon that transversal membrane asymmetry is the common required element for the formation of membrane curvature. The present study demonstrates that elevating proton concentration at the cell surface stimulates the formation of membrane invaginations and vesiculation accompanied by efficient uptake of macromolecules (Dextran-FITC, 70 kD), relative to the constitutive one. The insensitivity of proton induced uptake to inhibiting treatments and agents of the known endocytic pathways suggests the entry of macromolecules to proceeds via a yet undefined route. This is in line with the fact that neither ATP depletion, nor the lowering of temperature, abolishes the uptake process. In addition, fusion mechanism such as associated with low pH uptake of toxins and viral proteins can be disregarded by employing the polysaccharide dextran as the uptake molecule. The proton induced uptake increases linearly in the extracellular pH range of 6.5 to 4.5, and possesses a steep increase at the range of 4> pH>3, reaching a plateau at pH≤3. The kinetics of the uptake implies that the induced vesicles release their content to the cytosol and undergo rapid recycling to the plasma membrane. We suggest that protonation of the cell’s surface induces local charge asymmetries across the cell membrane bilayer, inducing inward curvature of the cell membrane and consequent vesiculation and uptake
Combination therapy with oral treprostinil for pulmonary arterial hypertension. A double-blind placebo-controlled clinical trial
Rationale: Oral treprostinil improves exercise capacity in patients with pulmonary arterial hypertension (PAH), but the effect on clinical outcomes was unknown.
Objectives: To evaluate the effect of oral treprostinil compared with placebo on time to first adjudicated clinical worsening event in participants with PAH who recently began approved oral monotherapy.
Methods: In this event-driven, double-blind study, we randomly allocated 690 participants (1:1 ratio) with PAH to receive placebo or oral treprostinil extended-release tablets three times daily. Eligible participants were using approved oral monotherapy for over 30 days before randomization and had a 6-minute-walk distance 150 m or greater. The primary endpoint was the time to first adjudicated clinical worsening event: death; hospitalization due to worsening PAH; initiation of inhaled or parenteral prostacyclin therapy; disease progression; or unsatisfactory long-term clinical response.
Measurements and Main Results: Clinical worsening occurred in 26% of the oral treprostinil group compared with 36% of placebo participants (hazard ratio, 0.74; 95% confidence interval, 0.56–0.97; P = 0.028). Key measures of disease status, including functional class, Borg dyspnea score, and N-terminal pro–brain natriuretic peptide, all favored oral treprostinil treatment at Week 24 and beyond. A noninvasive risk stratification analysis demonstrated that oral treprostinil–assigned participants had a substantially higher mortality risk at baseline but achieved a lower risk profile from Study Weeks 12–60. The most common adverse events in the oral treprostinil group were headache, diarrhea, flushing, nausea, and vomiting.
Conclusions: In participants with PAH, addition of oral treprostinil to approved oral monotherapy reduced the risk of clinical worsening.
Clinical trial registered with www.clinicaltrials.gov (NCT01560624)
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