Slim LSTM networks: LSTM_6 and LSTM_C6

We have shown previously that our parameter-reduced variants of Long Short-Term Memory (LSTM) Recurrent Neural Networks (RNN) are comparable in performance to the standard LSTM RNN on the MNIST dataset. In this study, we show that this is also the case for two diverse benchmark datasets, namely, the review sentiment IMDB and the 20 Newsgroup datasets. Specifically, we focus on two of the simplest variants, namely LSTM_6 (i.e., standard LSTM with three constant fixed gates) and LSTM_C6 (i.e., LSTM_6 with further reduced cell body input block). We demonstrate that these two aggressively reduced-parameter variants are competitive with the standard LSTM when hyper-parameters, e.g., learning parameter, number of hidden units and gate constants are set properly. These architectures enable speeding up training computations and hence, these networks would be more suitable for online training and inference onto portable devices with relatively limited computational resources.Comment: 6 pages, 12 figures, 5 table

Synthesis, characterization, bioactivity and biocompatibility of nanostructured materials based on the wollastonite-poly(ethylmethacrylate-co-vinylpyrrolidone) system

Composite materials are very promising biomaterials for hard tissue augmentation. The approach assayed in this work involves the manufacturing of a composite made of a bioactive ceramic, natural wollastonite (W) and a nanostructured copolymer of ethylmethacrylate (EMA) and vinylpyrrolidone (VP) to yield a bioresorbable and biocompatible VP–EMA copolymer. A bulk polymerization was induced thermally at 508C, using 1 wt % azobis(isobutyronitrile) (AIBN) as free-radical initiator. Structural characterization, compressive strength, flexural strength (FS), degradation, bioactivity, and biocompatibility were evaluated in specimens with a 60/40 VP/EMA ratio and ceramic content in the range 0–60%. A good integration between phases was achieved. Greater compression and FS, in comparison with the pure copolymer specimens was obtained only when the ceramic load got up to 60% of the total weight. The soaking in NaCl solution resulted in the initial swelling of the specimens tested. The maximum swelling was reached after 2–3 h of immersion and it was significantly greater for lower ceramic loads. This result makes the polymer component the main responsible for the interactions with the media. After soaking in SBF, microdomains segregation can be observed in the polymer component that can be related with a dramatic difference in the reactivity of both monomers in free radical polymerization, whereas the formation of an apatite-like layer on the W surfaces can be observed. Biocompatibility in vitro studies showed the absence of cytotoxicity of all formulations. The cells were able to adhere on the polystyrene negative control and on specimens containing 60 wt % wollastonite forming a monolayer and showing a normal morphology. However, a low cellular growth was observed. 2008 Wiley Periodicals, Inc. J Biomed Mater Res 88A: 53–64, 2009Peer reviewe

Cell spotting: Educational and motivational outcomes of cell biology citizen science project in the classroom

Success stories of citizen science projects widely demonstrate the value of this open science paradigm and encourage organizations to shift towards new ways of doing research. While benefits for researchers are clear, outcomes for individuals participating in these projects are not easy to assess. The wide spectrum of volunteers collaborating in citizen science projects greatly contributes to the difficulty in the evaluation of the projects'' outcomes. Given the strong links between many citizen science projects and education, in this work we present an experience with hundreds of students (aged 15-18) of two different countries who participate in a project on cell biology research-Cell Spotting-as part of their regular classroom activities. Apart from introducing the project and resources involved, we aim to provide an overview of the benefits of integrating citizen science in the context of formal science education and of what teachers and students may obtain from it. In this case, besides helping students to consolidate and apply theoretical concepts included in the school curriculum, some other types of informal learning have also been observed such as the feeling of playing a key role, which contributed to an increase of students'' motivation

Self-acetylation at the active site of phosphoenolpyruvate carboxykinase (PCK1) controls enzyme activity

Acetylation is known to regulate the activity of cytosolic phosphoenolpyruvate carboxykinase (PCK1), a key enzyme in gluconeogenesis, by promoting the reverse reaction of the enzyme (converting phosphoenolpyruvate to oxaloacetate). It is also known that the histone acetyltransferase p300 can induce PCK1 acetylation in cells, but whether that is a direct or indirect function was not known. Here we initially set out to determine whether p300 can acetylate directly PCK1 in vitro. We report that p300 weakly acetylates PCK1, but surprisingly, using several techniques including protein crystallization, mass spectrometry, isothermal titration calorimetry, saturation-transfer difference nuclear magnetic resonance and molecular docking, we found that PCK1 is also able to acetylate itself using acetyl-CoA independently of p300. This reaction yielded an acetylated recombinant PCK1 with a 3-fold decrease in kcat without changes in Km for all substrates. Acetylation stoichiometry was determined for 14 residues, including residues lining the active site. Structural and kinetic analyses determined that site-directed acetylation of K244, located inside the active site, altered this site and rendered the enzyme inactive. In addition, we found that acetyl-CoA binding to the active site is specific and metal dependent. Our findings provide direct evidence for acetyl-CoA binding and chemical reaction with the active site of PCK1 and suggest a newly discovered regulatory mechanism of PCK1 during metabolic stress

Systemic epidermal nevus with involvement of the oral mucosa due to FGFR3 mutation

Our results show that activating FGFR3 mutations can also affect the oral mucosa and that extracutaneous manifestations of EN syndrome can be subtle. We highlight the theoretical risk of the patient having an offspring with thanatophoric dysplasia as gonadal mosaicism for the R248C mutation cannot be excluded

Koilocytes indicate a role for human papilloma virus in breast cancer

Background: High-risk human papilloma viruses (HPVs) are candidates as causal viruses in breast cancer. The scientific challenge is to determine whether HPVs are causal and not merely passengers or parasites. Studies of HPV-related koilocytes in breast cancer offer an opportunity to address this crucial issue. Koilocytes are epithelial cells characterised by perinuclear haloes surrounding condensed nuclei and are commonly present in cervical intraepithelial neoplasia. Koilocytosis is accepted as pathognomonic (characteristic of a particular disease) of HPV infection. The aim of this investigation is to determine whether putative koilocytes in normal and malignant breast tissues are because of HPV infection. Methods: Archival formalin-fixed normal and malignant breast specimens were investigated by histology, in situ PCR with confirmation of the findings by standard PCR and sequencing of the products, plus immunohistochemistry to identify HPV E6 oncoproteins. Results: human papilloma virus-associated koilocytes were present in normal breast skin and lobules and in the breast skin and cancer tissue of patients with ductal carcinoma in situ (DCIS) and invasive ductal carcinomas (IDCs). Interpretation: As koilocytes are known to be the precursors of some HPV-associated cervical cancer, it follows that HPVs may be causally associated with breast cancer.6 page(s

Number and mode of inheritance of QTL influencing backfat thickness on SSC2p in Sino-European pig pedigrees

<p>Abstract</p> <p>Background</p> <p>In the pig, multiple QTL associated with growth and fatness traits have been mapped to chromosome 2 (SSC2) and among these, at least one shows paternal expression due to the IGF2-intron3-G3072A substitution. Previously published results on the position and imprinting status of this QTL disagree between analyses from French and Dutch F2 crossbred pig populations obtained with the same breeds (Meishan crossed with Large White or Landrace).</p> <p>Methods</p> <p>To study the role of paternal and maternal alleles at the IGF2 locus and to test the hypothesis of a second QTL affecting backfat thickness on the short arm of SSC2 (SSC2p), a QTL mapping analysis was carried out on a combined pedigree including both the French and Dutch F2 populations, on the progeny of F1 males that were heterozygous (A/G) and homozygous (G/G) at the IGF2 locus. Simulations were performed to clarify the relations between the two QTL and to understand to what extent they can explain the discrepancies previously reported.</p> <p>Results</p> <p>The QTL analyses showed the segregation of at least two QTL on chromosome 2 in both pedigrees, i.e. the IGF2 locus and a second QTL segregating at least in the G/G F1 males and located between positions 30 and 51 cM. Statistical analyses highlighted that the maternally inherited allele at the IGF2 locus had a significant effect but simulation studies showed that this is probably a spurious effect due to the segregation of the second QTL.</p> <p>Conclusions</p> <p>Our results show that two QTL on SSC2p affect backfat thickness. Differences in the pedigree structures and in the number of heterozygous females at the IGF2 locus result in different imprinting statuses in the two pedigrees studied. The spurious effect observed when a maternally allele is present at the IGF2 locus, is in fact due to the presence of a second closely located QTL. This work confirms that pig chromosome 2 is a major region associated with fattening traits.</p

C-Terminal Extension of the Yeast Mitochondrial DNA Polymerase Determines the Balance between Synthesis and Degradation

Saccharomyces cerevisiae mitochondrial DNA polymerase (Mip1) contains a C-terminal extension (CTE) of 279 amino acid residues. The CTE is required for mitochondrial DNA maintenance in yeast but is absent in higher eukaryotes. Here we use recombinant Mip1 C-terminal deletion mutants to investigate functional importance of the CTE. We show that partial removal of the CTE in Mip1Δ216 results in strong preference for exonucleolytic degradation rather than DNA polymerization. This disbalance in exonuclease and polymerase activities is prominent at suboptimal dNTP concentrations and in the absence of correctly pairing nucleotide. Mip1Δ216 also displays reduced ability to synthesize DNA through double-stranded regions. Full removal of the CTE in Mip1Δ279 results in complete loss of Mip1 polymerase activity, however the mutant retains its exonuclease activity. These results allow us to propose that CTE functions as a part of Mip1 polymerase domain that stabilizes the substrate primer end at the polymerase active site, and is therefore required for efficient mitochondrial DNA replication in vivo

Positive Darwinian Selection in the Piston That Powers Proton Pumps in Complex I of the Mitochondria of Pacific Salmon

The mechanism of oxidative phosphorylation is well understood, but evolution of the proteins involved is not. We combined phylogenetic, genomic, and structural biology analyses to examine the evolution of twelve mitochondrial encoded proteins of closely related, yet phenotypically diverse, Pacific salmon. Two separate analyses identified the same seven positively selected sites in ND5. A strong signal was also detected at three sites of ND2. An energetic coupling analysis revealed several structures in the ND5 protein that may have co-evolved with the selected sites. These data implicate Complex I, specifically the piston arm of ND5 where it connects the proton pumps, as important in the evolution of Pacific salmon. Lastly, the lineage to Chinook experienced rapid evolution at the piston arm