Simple and Effective Multi-Paragraph Reading Comprehension

We consider the problem of adapting neural paragraph-level question answering models to the case where entire documents are given as input. Our proposed solution trains models to produce well calibrated confidence scores for their results on individual paragraphs. We sample multiple paragraphs from the documents during training, and use a shared-normalization training objective that encourages the model to produce globally correct output. We combine this method with a state-of-the-art pipeline for training models on document QA data. Experiments demonstrate strong performance on several document QA datasets. Overall, we are able to achieve a score of 71.3 F1 on the web portion of TriviaQA, a large improvement from the 56.7 F1 of the previous best system.Comment: 11 pages, updated a referenc

Structural, molecular motions, and free-energy landscape of <i>Leishmania</i> sterol-14α-demethylase wild type and drug resistant mutant: a comparative molecular dynamics study

<p>Sterol-14α-demethylase (CYP51) is an ergosterol pathway enzyme crucial for the survival of infectious <i>Leishmania</i> parasite. Recent high-throughput metabolomics and whole genome sequencing study revealed amphotericin B resistance in <i>Leishmania</i> is indeed due to mutation in CYP51. The residue of mutation (asparagine 176) is conserved across the kinetoplastidae and not in yeast or humans, portraying its functional significance. In order to understand the possible cause for the resistance, knowledge of structural changes due to mutation is of high importance. To shed light on the structural changes of wild and mutant CYP51, we conducted comparative molecular dynamics simulation study. The active site, substrate biding cavity, substrate channel entrance (SCE), and cavity involving the mutated site were studied based on basic parameters and large concerted molecular motions derived from essential dynamics analyses of 100 ns simulation. Results indicated that mutant CYP51 is stable and less compact than the wild type. Correspondingly, the solvent accessible surface area (SASA) of the mutant was found to be increased, especially in active site and cavities not involving the mutation site. Free-energy landscape analysis disclosed mutant to have a rich conformational diversity than wild type, with various free-energy conformations of mutant having SASA greater than wild type with SCE open. More residues were found to interact with the mutant CYP51 upon docking of substrate to both the wild and mutant CYP51. These results indicate that, relative to wild type, the N176I mutation of CYP51 in <i>Leishmania mexicana</i> could possibly favor increased substrate binding efficiency.</p

HAT2 mediates histone H4K4 acetylation and affects micrococcal nuclease sensitivity of chromatin in <i>Leishmania donovani</i>

<div><p>Histone post-translational modifications (PTMs) such as acetylation and methylation are known to affect chromatin higher order structures. Primary targets of these modifications include basic residues present at N-terminus tail region of core histones. Four histone acetyltransferase (HAT) genes have been identified in trypanosomatids. HAT1, HAT3 and HAT4 of <i>Leishmania donovani</i> have been partially characterized. However, there is no report about HAT2 of <i>Leishmania donovani</i>. Lysine residues present on the N-terminal tail of <i>Leishmania donovani</i> histone H4 are conserved in other trypanosomatids and humans. PTMs of lysines modulate various functions at chromatin level. The four histone acetyltransferases encoded in Leishmania genome were over-expressed to analyse their functional activity. All four HATs were found actively acetylating core histones H3/H4. Similar to <i>L</i>. <i>donovani</i> HAT3 and HAT4, HAT2 was found to be a member of MYST family protein and have SAS2 type domain. Over-expression of HAT2 significantly increases acetylation of H4K4. To analyse the effect of HAT2 over-expression on chromatin accessibility, micrococcal nuclease digestion assay was performed. MNase digestion resulted in a higher proportion of the mononucleosomes and dinucleosomes in HAT2 over-expressing cells as compared to WT <i>L</i>. <i>donovani</i> cells. Acetylation of lysine-4 neutralizes the amino terminal region of histone H4. This weakens its interaction with neighbouring nucleosomes and the linker DNA. HAT2 over-expression in <i>L</i>. <i>donovani</i> resulted in highly accessible chromatin suggesting chromatin decondensation. HAT2 may have an important role to play in global regulation of transcription in <i>L</i>. <i>donovani</i>. Better understanding of these epigenetic determinants of parasite would help in designing novel therapeutic strategies.</p></div

Number of visceral leishmaniasis cases in 2009 and 2010 in all the PHCs of Muzaffarpur and Saran disctricts indicating the highest number of cases in Paroo and Sahebganj of Muzaffarpur district and Baniyapur and Marhoura of Saran district.

<p>Number of visceral leishmaniasis cases in 2009 and 2010 in all the PHCs of Muzaffarpur and Saran disctricts indicating the highest number of cases in Paroo and Sahebganj of Muzaffarpur district and Baniyapur and Marhoura of Saran district.</p

ASHA knowledge in Control (untrained) and Intervention (trained) PHC.

<p>Difference between intervention and control groups for all indicators was p<0.05.</p

VL cases referred by ASHAs before and after training.

1<p>The total number of cases in 2011 is more than that in 2012. This was because in 2011, cases from 12 months were followed-up, whereas in 2012, cases from only 6 months were followed-up. The increased recruitment rate between 2011 and 2012 observed in the intervention PHCs, Paroo and Marhoura was statistically significant (p<0.05).</p>2<p>Numbers in brackets represent the number of cases after removing the 14 cases that were referred by the ASHA from Tarawa village that received knowledge about VL from the study team in 2011. The increased recruitment rate at Sahebganj PHC between 2011 and 2012 was significant (p<0.05), but was not significant after removal of the 14 cases from Tarawa (p = 0.12).</p

Duration of fever before seeking treatment at the PHC.

<p>Duration of fever before seeking treatment at the PHC.</p