The AFLOW Fleet for Materials Discovery

The traditional paradigm for materials discovery has been recently expanded to incorporate substantial data driven research. With the intent to accelerate the development and the deployment of new technologies, the AFLOW Fleet for computational materials design automates high-throughput first principles calculations, and provides tools for data verification and dissemination for a broad community of users. AFLOW incorporates different computational modules to robustly determine thermodynamic stability, electronic band structures, vibrational dispersions, thermo-mechanical properties and more. The AFLOW data repository is publicly accessible online at aflow.org, with more than 1.7 million materials entries and a panoply of queryable computed properties. Tools to programmatically search and process the data, as well as to perform online machine learning predictions, are also available.Comment: 14 pages, 8 figure

X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes

X-linked intellectual disability (XLID) is a clinically and genetically heterogeneous disorder. During the past two decades in excess of 100 X-chromosome ID genes have been identified. Yet, a large number of families mapping to the X-chromosome remained unresolved suggesting that more XLID genes or loci are yet to be identified. Here, we have investigated 405 unresolved families with XLID. We employed massively parallel sequencing of all X-chromosome exons in the index males. The majority of these males were previously tested negative for copy number variations and for mutations in a subset of known XLID genes by Sanger sequencing. In total, 745 X-chromosomal genes were screened. After stringent filtering, a total of 1297 non-recurrent exonic variants remained for prioritization. Co-segregation analysis of potential clinically relevant changes revealed that 80 families (20%) carried pathogenic variants in established XLID genes. In 19 families, we detected likely causative protein truncating and missense variants in 7 novel and validated XLID genes (CLCN4, CNKSR2, FRMPD4, KLHL15, LAS1L, RLIM and USP27X) and potentially deleterious variants in 2 novel candidate XLID genes (CDK16 and TAF1). We show that the CLCN4 and CNKSR2 variants impair protein functions as indicated by electrophysiological studies and altered differentiation of cultured primary neurons from Clcn4−/− mice or after mRNA knock-down. The newly identified and candidate XLID proteins belong to pathways and networks with established roles in cognitive function and intellectual disability in particular. We suggest that systematic sequencing of all X-chromosomal genes in a cohort of patients with genetic evidence for X-chromosome locus involvement may resolve up to 58% of Fragile X-negative cases

The N-terminus of FILIA Forms an Atypical KH Domain with a Unique Extension Involved in Interaction with RNA

FILIA is a member of the recently identified oocyte/embryo expressed gene family in eutherian mammals, which is characterized by containing an N-terminal atypical KH domain. Here we report the structure of the N-terminal fragment of FILIA (FILIA-N), which represents the first reported three-dimensional structure of a KH domain in the oocyte/embryo expressed gene family of proteins. The structure of FILIA-N revealed a unique N-terminal extension beyond the canonical KH region, which plays important roles in interaction with RNA. By co-incubation with the lysates of mice ovaries, FILIA and FILIA-N could sequester specific RNA components, supporting the critical roles of FILIA in regulation of RNA transcripts during mouse oogenesis and early embryogenesis

Immunization with a Borrelia burgdorferi BB0172-Derived Peptide Protects Mice against Lyme Disease

Lyme disease is the most prevalent arthropod borne disease in the US and it is caused by the bacterial spirochete Borrelia burgdorferi (Bb), which is acquired through the bite of an infected Ixodes tick. Vaccine development efforts focused on the von Willebrand factor A domain of the borrelial protein BB0172 from which four peptides (A, B, C and D) were synthesized and conjugated to Keyhole Limpet Hemocyanin, formulated in Titer Max® adjuvant and used to immunize C3H/HeN mice subcutaneously at days 0, 14 and 21. Sera were collected to evaluate antibody responses and some mice were sacrificed for histopathology to evaluate vaccine safety. Twenty-eight days post-priming, protection was evaluated by needle inoculation of half the mice in each group with 103 Bb/mouse, whereas the rest were challenged with 105Bb/mouse. Eight weeks post-priming, another four groups of similarly immunized mice were challenged using infected ticks. In both experiments, twenty-one days post-challenge, the mice were sacrificed to determine antibody responses, bacterial burdens and conduct histopathology. Results showed that only mice immunized with peptide B were protected against challenge with Bb. In addition, compared to the other the treatment groups, peptide B-immunized mice showed very limited inflammation in the heart and joint tissues. Peptide B-specific antibody titers peaked at 8 weeks post-priming and surprisingly, the anti-peptide B antibodies did not cross-react with Bb lysates. These findings strongly suggest that peptide B is a promising candidate for the development of a new DIVA vaccine (Differentiate between Infected and Vaccinated Animals) for protection against Lyme disease.The open access fee for this work was funded through the Texas A&M University Open Access to Knowledge (OAK) Fund

Autothermal reforming of palm empty fruit bunch bio-oil: thermodynamic modelling

This work focuses on thermodynamic analysis of the autothermal reforming of palm empty fruit bunch (PEFB) bio-oil for the production of hydrogen and syngas. PEFB bio-oil composition was simulated using bio-oil surrogates generated from a mixture of acetic acid, phenol, levoglucosan, palmitic acid and furfural. A sensitivity analysis revealed that the hydrogen and syngas yields were not sensitive to actual bio-oil composition, but were determined by a good match of molar elemental composition between real bio-oil and surrogate mixture. The maximum hydrogen yield obtained under constant reaction enthalpy and pressure was about 12 wt% at S/C = 1 and increased to about 18 wt% at S/C = 4; both yields occurring at equivalence ratio Φ of 0.31. The possibility of generating syngas with varying H2 and CO content using autothermal reforming was analysed and application of this process to fuel cells and Fischer-Tropsch synthesis is discussed. Using a novel simple modelling methodology, reaction mechanisms were proposed which were able to account for equilibrium product distribution. It was evident that different combinations of reactions could be used to obtain the same equilibrium product concentrations. One proposed reaction mechanism, referred to as the ‘partial oxidation based mechanism’ involved the partial oxidation reaction of the bio-oil to produce hydrogen, with the extent of steam reforming and water gas shift reactions varying depending on the amount of oxygen used. Another proposed mechanism, referred to as the ‘complete oxidation based mechanism’ was represented by thermal decomposition of about 30% of bio-oil and hydrogen production obtained by decomposition, steam reforming, water gas shift and carbon gasification reactions. The importance of these mechanisms in assisting in the eventual choice of catalyst to be used in a real ATR of PEFB bio-oil process was discussed