Computability of ordinary differential equations

In this paper we provide a brief review of several results about the computability of initial-value problems (IVPs) defined with ordinary differential equations (ODEs). We will consider a variety of settings and analyze how the computability of the IVP will be affected. Computational complexity results will also be presented, as well as computable versions of some classical theorems about the asymptotic behavior of ODEs.info:eu-repo/semantics/publishedVersio

Value of prominent flow voids without cord edema in the detection of spinal arteriovenous fistulae

Purpose: To determine the prevalence of spinal dural arteriovenous fistulae (SDAVF) in patients presenting with prominent vascular flow voids on imaging without other imaging findings suggestive of SDAVF. Methods: We retrospectively identified patients from January 1, 2005 to March 1, 2012 who underwent spinal angiography for suspected SDAVF with prominent vascular flow voids on prior imaging. We excluded patients with other major spinal pathology or other imaging findings of SDAVF including cord hyperintensity, enhancement, or expansion. We calculated the proportion of patients with positive findings for SDAVF on angiography and evaluated the prevalence of SDAVF for this finding alone and in correlation with clinical findings. Results: 18 patients underwent spinal angiography for prominent flow voids on imaging without other spinal pathology or imaging findings of SDAVF. Three had a SDAVF detected on angiography. The prevalence of SDAVF in this population was low, only 17% (95% CI 6-39%). All of the patients with positive angiography findings had myelopathy, increasing the prevalence to 100% if the additional clinical finding of myelopathy was present. Conclusions: Prominent flow voids without other imaging findings suggestive of SDAVF is poorly predictive of the presence of a SDAVF, unless myelopathy is present clinically. © 2014 Alhilali et al

Deficiency of FLCN in Mouse Kidney Led to Development of Polycystic Kidneys and Renal Neoplasia

The Birt–Hogg–Dubé (BHD) disease is a genetic cancer syndrome. The responsible gene, BHD, has been identified by positional cloning and thought to be a novel tumor suppressor gene. BHD mutations cause many types of diseases including renal cell carcinomas, fibrofolliculomas, spontaneous pneumothorax, lung cysts, and colonic polyps/cancers. By combining Gateway Technology with the Ksp-Cre gene knockout system, we have developed a kidney-specific BHD knockout mouse model. BHDflox/flox/Ksp-Cre mice developed enlarged kidneys characterized by polycystic kidneys, hyperplasia, and cystic renal cell carcinoma. The affected BHDflox/flox/Ksp-Cre mice died of renal failure at approximate three weeks of age, having blood urea nitrogen levels over tenfold higher than those of BHD flox/+/Ksp-Cre and wild-type littermate controls. We further demonstrated that these phenotypes were caused by inactivation of BHD and subsequent activation of the mTOR pathway. Application of rapamycin, which inhibits mTOR activity, to the affected mice led to extended survival and inhibited further progression of cystogenesis. These results provide a correlation of kidney-targeted gene inactivation with renal carcinoma, and they suggest that the BHD product FLCN, functioning as a cyst and tumor suppressor, like other hamartoma syndrome–related proteins such as PTEN, LKB1, and TSC1/2, is a component of the mTOR pathway, constituting a novel FLCN-mTOR signaling branch that regulates cell growth/proliferation

A Porcine Adenovirus with Low Human Seroprevalence Is a Promising Alternative Vaccine Vector to Human Adenovirus 5 in an H5N1 Virus Disease Model

Human adenovirus 5 (AdHu5) vectors are robust vaccine platforms however the presence of naturally-acquired neutralizing antibodies may reduce vector efficacy and potential for re-administration. This study evaluates immune responses and protection following vaccination with a replication-incompetent porcine adenovirus 3 (PAV3) vector as an alternative vaccine to AdHu5 using an avian influenza H5N1 disease model. Vaccine efficacy was evaluated in BALB/c mice following vaccination with different doses of the PAV3 vector expressing an optimized A/Hanoi/30408/2005 H5N1 hemagglutinin antigen (PAV3-HA) and compared with an AdHu5-HA control. PAV3-HA rapidly generated antibody responses, with significant neutralizing antibody titers on day 21, and stronger cellular immune responses detected on day 8, compared to AdHu5-HA. The PAV3-HA vaccine, administered 8 days before challenge, demonstrated improved survival and lower virus load. Evaluation of long-term vaccine efficacy at 12 months post-vaccination showed better protection with the PAV3-HA than with the AdHu5-HA vaccine. Importantly, as opposed to AdHu5, PAV3 vector was not significantly neutralized by human antibodies pooled from over 10,000 individuals. Overall, PAV3-based vector is capable of mediating swift, strong immune responses and offer a promising alternative to AdHu5

Demographic and spatial predictors of anemia in women of reproductive age in Timor-Leste: Implications for health program prioritization

10.1371/journal.pone.0091252PLoS ONE93-POLN

Human Fatal Zaire Ebola Virus Infection Is Associated with an Aberrant Innate Immunity and with Massive Lymphocyte Apoptosis

Ebolavirus, especially the species Zaïre (ZEBOV), causes a fulminating hemorrhagic fever syndrome resulting in the death of most patients within a few days. In vitro studies and animal models have brought some insight as to the immune responses to ZEBOV infection. However, human immune responses have as yet been poorly investigated, mainly due to the fact that most outbreaks occur in remote areas of central Africa. Published studies, based on small numbers of biological samples have given conflicting results. We studied a unique collection of 50 blood samples obtained during five outbreaks that occurred between 1996 and 2003 in Gabon and Republic of Congo. We measured the plasma levels of 50 soluble factors known to be involved in immune responses to viral diseases. For the first time, using a cell staining technique, we analyzed circulating lymphocytes from ZEBOV-infected patients. We found that fatal outcome in humans is associated with aberrant innate immunity characterized by a “cytokine storm,” with hypersecretion of numerous proinflammatory mediators and by the noteworthy absence of antiviral interferon. The adaptive response is globally suppressed, showing a massive loss of CD4 and CD8 lymphocytes and the immune mediators they produce. These findings may have important pathological and therapeutic implications

AdS/CFT beyond the unitarity bound

Scalars in AdS${}_{d+1}$ with squared masses in the Breitenlohner-Freedman window $-d^2/4 \le m^2 < -d^2/4 +1$ (in units with the AdS scale $\ell$ set to 1) are known to enjoy a variety of boundary conditions. For larger masses $m^2 > -d^2/4 +1$, unitarity bounds in possible dual CFTs suggest that such general boundary conditions should lead to ghosts. We show that this is not always the case as, for conformally-invariant boundary conditions in Poincar\'e AdS that would naively violate unitarity bounds, the system is generically ghost-free. Conflicts with unitarity bounds are avoided due to the presence of unexpected pure gauge modes and an associated infrared divergence. The expected ghosts appear when the IR divergence is removed either by deforming these boundary conditions or considering global AdS.Comment: 24 page

Genome-Wide Analysis of Müller Glial Differentiation Reveals a Requirement for Notch Signaling in Postmitotic Cells to Maintain the Glial Fate

Previous studies have shown that Müller glia are closely related to retinal progenitors; these two cell types express many of the same genes and after damage to the retina, Müller glia can serve as a source for new neurons, particularly in non-mammalian vertebrates. We investigated the period of postnatal retinal development when progenitors are differentiating into Müller glia to better understand this transition. FACS purified retinal progenitors and Müller glia from various ages of Hes5-GFP mice were analyzed by Affymetrix cDNA microarrays. We found that genes known to be enriched/expressed by Müller glia steadily increase over the first three postnatal weeks, while genes associated with the mitotic cell cycle are rapidly downregulated from P0 to P7. Interestingly, progenitor genes not directly associated with the mitotic cell cycle, like the proneural genes Ascl1 and Neurog2, decline more slowly over the first 10–14 days of postnatal development, and there is a peak in Notch signaling several days after the presumptive Müller glia have been generated. To confirm that Notch signaling continues in the postmitotic Müller glia, we performed in situ hybridization, immunolocalization for the active form of Notch, and immunofluorescence for BrdU. Using genetic and pharmacological approaches, we found that sustained Notch signaling in the postmitotic Müller glia is necessary for their maturation and the stabilization of the glial identity for almost a week after the cells have exited the mitotic cell cycle