Why Spiking Neural Networks Are Efficient: A Theorem

Current artificial neural networks are very successful in many machine learning applications, but in some cases they still lag behind human abilities. To improve their performance, a natural idea is to simulate features of biological neurons which are not yet implemented in machine learning. One of such features is the fact that in biological neural networks, signals are represented by a train of spikes. Researchers have tried adding this spikiness to machine learning and indeed got very good results, especially when processing time series (and, more generally, spatio-temporal data). In this paper, we provide a theoretical explanation for this empirical success

Theoretical size distribution of fossil taxa: analysis of a null model

BACKGROUND: This article deals with the theoretical size distribution (of number of sub-taxa) of a fossil taxon arising from a simple null model of macroevolution. MODEL: New species arise through speciations occurring independently and at random at a fixed probability rate, while extinctions either occur independently and at random (background extinctions) or cataclysmically. In addition new genera are assumed to arise through speciations of a very radical nature, again assumed to occur independently and at random at a fixed probability rate. CONCLUSION: The size distributions of the pioneering genus (following a cataclysm) and of derived genera are determined. Also the distribution of the number of genera is considered along with a comparison of the probability of a monospecific genus with that of a monogeneric family

Identification and characterization of a novel non-structural protein of bluetongue virus

Bluetongue virus (BTV) is the causative agent of a major disease of livestock (bluetongue). For over two decades, it has been widely accepted that the 10 segments of the dsRNA genome of BTV encode for 7 structural and 3 non-structural proteins. The non-structural proteins (NS1, NS2, NS3/NS3a) play different key roles during the viral replication cycle. In this study we show that BTV expresses a fourth non-structural protein (that we designated NS4) encoded by an open reading frame in segment 9 overlapping the open reading frame encoding VP6. NS4 is 77–79 amino acid residues in length and highly conserved among several BTV serotypes/strains. NS4 was expressed early post-infection and localized in the nucleoli of BTV infected cells. By reverse genetics, we showed that NS4 is dispensable for BTV replication in vitro, both in mammalian and insect cells, and does not affect viral virulence in murine models of bluetongue infection. Interestingly, NS4 conferred a replication advantage to BTV-8, but not to BTV-1, in cells in an interferon (IFN)-induced antiviral state. However, the BTV-1 NS4 conferred a replication advantage both to a BTV-8 reassortant containing the entire segment 9 of BTV-1 and to a BTV-8 mutant with the NS4 identical to the homologous BTV-1 protein. Collectively, this study suggests that NS4 plays an important role in virus-host interaction and is one of the mechanisms played, at least by BTV-8, to counteract the antiviral response of the host. In addition, the distinct nucleolar localization of NS4, being expressed by a virus that replicates exclusively in the cytoplasm, offers new avenues to investigate the multiple roles played by the nucleolus in the biology of the cell

Surgery, with or without tamoxifen, vs tamoxifen alone for older women with operable breast cancer: Cochrane review

The published literature comparing surgery, with or without adjuvant endocrine therapy, with endocrine therapy alone in older women with operable breast cancer was systematically reviewed.The design used is Cochrane review. Randomised controlled trials retrieved from the Cochrane Breast Cancer Group Specialised Register on 29 June 2005. Eligible studies recruited women aged 70 years or over with operable breast cancer, fit for surgery under general anaesthia. The studies compared surgery (either mastectomy or wide local excision, with or without endocrine therapy) to endocrine therapy alone. Primary outcomes were overall survival (OS) and progression-free survival (PFS). Double data extraction and quality assessment were undertaken. Seven eligible trials were identified of which six had published time-to-event data. The quality of the allocation concealment was adequate in three studies and unclear in the remainder. In each case the endocrine therapy used was tamoxifen. When surgery alone was compared to endocrine therapy alone, there was no significant difference in OS (hazard ratio (HR) 0.98, 95% confidence interval (CI) 0.74–1.30, P=0.9), but a significant difference in PFS (HR 0.55, 95% CI 0.39–0.77, P=0.0006). When surgery with adjuvant endocrine therapy was compared to endocrine therapy alone, there was no significant difference in OS (HR 0.86, 95% CI 0.73–1.00, P=0.06), but a significant difference in PFS (HR 0.65 (95% CI 0.53–0.81, P=0.0001) for surgery plus endocrine therapy vs primary endocrine. The regimens have different side effect profiles with one study suggesting increased psychosocial morbidity at 3 months in the surgical arm, which resolves by 2 years. Primary endocrine therapy with tamoxifen is associated with inferior local disease control but non-inferior survival to surgery for breast cancer in older women. Trials are needed to evaluate appropriate selection criteria for its use in terms of patient co-morbidity and quality of life. Trials are needed to evaluate the clinical effectiveness of aromatase inhibitors as primary therapy for this population

Acid Stability of the Hemagglutinin Protein Regulates H5N1 Influenza Virus Pathogenicity

Highly pathogenic avian influenza viruses of the H5N1 subtype continue to threaten agriculture and human health. Here, we use biochemistry and x-ray crystallography to reveal how amino-acid variations in the hemagglutinin (HA) protein contribute to the pathogenicity of H5N1 influenza virus in chickens. HA proteins from highly pathogenic (HP) A/chicken/Hong Kong/YU562/2001 and moderately pathogenic (MP) A/goose/Hong Kong/437-10/1999 isolates of H5N1 were found to be expressed and cleaved in similar amounts, and both proteins had similar receptor-binding properties. However, amino-acid variations at positions 104 and 115 in the vestigial esterase sub-domain of the HA1 receptor-binding domain (RBD) were found to modulate the pH of HA activation such that the HP and MP HA proteins are activated for membrane fusion at pH 5.7 and 5.3, respectively. In general, an increase in H5N1 pathogenicity in chickens was found to correlate with an increase in the pH of HA activation for mutant and chimeric HA proteins in the observed range of pH 5.2 to 6.0. We determined a crystal structure of the MP HA protein at 2.50 Å resolution and two structures of HP HA at 2.95 and 3.10 Å resolution. Residues 104 and 115 that modulate the acid stability of the HA protein are situated at the N- and C-termini of the 110-helix in the vestigial esterase sub-domain, which interacts with the B loop of the HA2 stalk domain. Interactions between the 110-helix and the stalk domain appear to be important in regulating HA protein acid stability, which in turn modulates influenza virus replication and pathogenesis. Overall, an optimal activation pH of the HA protein is found to be necessary for high pathogenicity by H5N1 influenza virus in avian species

Massive stars as thermonuclear reactors and their explosions following core collapse

Nuclear reactions transform atomic nuclei inside stars. This is the process of stellar nucleosynthesis. The basic concepts of determining nuclear reaction rates inside stars are reviewed. How stars manage to burn their fuel so slowly most of the time are also considered. Stellar thermonuclear reactions involving protons in hydrostatic burning are discussed first. Then I discuss triple alpha reactions in the helium burning stage. Carbon and oxygen survive in red giant stars because of the nuclear structure of oxygen and neon. Further nuclear burning of carbon, neon, oxygen and silicon in quiescent conditions are discussed next. In the subsequent core-collapse phase, neutronization due to electron capture from the top of the Fermi sea in a degenerate core takes place. The expected signal of neutrinos from a nearby supernova is calculated. The supernova often explodes inside a dense circumstellar medium, which is established due to the progenitor star losing its outermost envelope in a stellar wind or mass transfer in a binary system. The nature of the circumstellar medium and the ejecta of the supernova and their dynamics are revealed by observations in the optical, IR, radio, and X-ray bands, and I discuss some of these observations and their interpretations.Comment: To be published in " Principles and Perspectives in Cosmochemistry" Lecture Notes on Kodai School on Synthesis of Elements in Stars; ed. by Aruna Goswami & Eswar Reddy, Springer Verlag, 2009. Contains 21 figure

Establishment of a Bluetongue Virus Infection Model in Mice that Are Deficient in the Alpha/Beta Interferon Receptor

Bluetongue (BT) is a noncontagious, insect-transmitted disease of ruminants caused by the bluetongue virus (BTV). A laboratory animal model would greatly facilitate the studies of pathogenesis, immune response and vaccination against BTV. Herein, we show that adult mice deficient in type I IFN receptor (IFNAR(−/−)) are highly susceptible to BTV-4 and BTV-8 infection when the virus is administered intravenously. Disease was characterized by ocular discharges and apathy, starting at 48 hours post-infection and quickly leading to animal death within 60 hours of inoculation. Infectious virus was recovered from the spleen, lung, thymus, and lymph nodes indicating a systemic infection. In addition, a lymphoid depletion in spleen, and severe pneumonia were observed in the infected mice. Furthermore, IFNAR(−/−) adult mice immunized with a BTV-4 inactivated vaccine showed the induction of neutralizing antibodies against BTV-4 and complete protection against challenge with a lethal dose of this virus. The data indicate that this mouse model may facilitate the study of BTV pathogenesis, and the development of new effective vaccines for BTV

Histological and immunohistochemical features of the spleen in persistent polyclonal B-cell lymphocytosis closely mimic splenic B-cell lymphoma

Persistent polyclonal B-cell lymphocytosis (PPBL) is rare and intriguing hematological disorder predominantly reported in young to middle- aged smoking women. It is characterized by persistent moderate polyclonal B-cell lymphocytosis with circulating hallmark binucleated lymphocytes and elevated polyclonal serum IgM. Most patients have benign clinical course on long-term follow-up. Some pathologic features of PPBL may resemble malignant lymphoma, including morphology as well as frequent cytogenetic and molecular abnormalities. Significant symptomatic splenomegaly requiring splenectomy is very unusual for this disorder; therefore there is a lack of descriptions of the morphologic features of the spleen in the literature. We present here one of the first detailed descriptions of the morphologic and immunohistochemical features of the spleen from a young female with PPBL who developed massive splenomegaly during 6-year follow up. Splenectomy was performed for symptomatic relief and suspicion of malignant process. The morphological and immunohistochemical features of the spleen closely mimicked involvement by B-cell lymphoma, however there was no monotypic surface light chain restriction seen by flow cytometry and no clonal rearrangement of IgH gene was detected by molecular analysis. Evaluating a splenectomy sample in cases like this may present a diagnostic challenge to pathologists. Therefore, correlation with B cell clonality studies (by flow cytometry and molecular analysis), clinical findings and peripheral blood morphology searching for characteristic binucleated lymphocytes is essential to avoid misdiagnosing this benign process as B-cell lymphoma. We also present here a literature review on pathogenesis of PPBL