Fermentation kinetics including product and substrate inhibitions plus biomass death: a mathematical analysis

Fermentation is generally modelled by kinetic equations giving the time evolutions for biomass, substrate, and product concentrations. Although these equations can be solved analytically in simple cases if substrate/product inhibition and biomass death are included, they are typically solved numerically. We propose an analytical treatment of the kinetic equations --including cell death and an arbitrary number of inhibitions-- in which constant yield needs not be assumed. Equations are solved in phase space, i.e. the biomass concentration is written explicitly as a function of the substrate concentration.Comment: 4 pages, 4 figure

Word Embeddings for Entity-annotated Texts

Learned vector representations of words are useful tools for many information retrieval and natural language processing tasks due to their ability to capture lexical semantics. However, while many such tasks involve or even rely on named entities as central components, popular word embedding models have so far failed to include entities as first-class citizens. While it seems intuitive that annotating named entities in the training corpus should result in more intelligent word features for downstream tasks, performance issues arise when popular embedding approaches are naively applied to entity annotated corpora. Not only are the resulting entity embeddings less useful than expected, but one also finds that the performance of the non-entity word embeddings degrades in comparison to those trained on the raw, unannotated corpus. In this paper, we investigate approaches to jointly train word and entity embeddings on a large corpus with automatically annotated and linked entities. We discuss two distinct approaches to the generation of such embeddings, namely the training of state-of-the-art embeddings on raw-text and annotated versions of the corpus, as well as node embeddings of a co-occurrence graph representation of the annotated corpus. We compare the performance of annotated embeddings and classical word embeddings on a variety of word similarity, analogy, and clustering evaluation tasks, and investigate their performance in entity-specific tasks. Our findings show that it takes more than training popular word embedding models on an annotated corpus to create entity embeddings with acceptable performance on common test cases. Based on these results, we discuss how and when node embeddings of the co-occurrence graph representation of the text can restore the performance.Comment: This paper is accepted in 41st European Conference on Information Retrieva

Development and psychometric evaluation of the PMR-Impact Scale: a new patient reported outcome measure for polymyalgia rheumatica.

OBJECTIVES: Polymyalgia rheumatica (PMR) causes pain, stiffness and disability in older adults. Measuring the impact of the condition from the patient's perspective is vital to high-quality research and patient-centred care, yet there are no validated patient-reported outcome measures (PROMs) for PMR. We set out to develop and psychometrically evaluate a PMR-specific PROM. METHODS: Two cross-sectional postal surveys of people with a confirmed diagnosis of PMR were used to provide data for field testing and psychometric evaluation. 256 participants completed the draft PROM. Distribution of item responses was examined and exploratory factor analysis and Rasch analysis were used to inform item reduction, formation of dimension structure and scoring system development. 179 participants completed the PROM at two-time points, along with comparator questionnaires and anchor questions. Test-retest reliability, construct validity and responsiveness were evaluated. RESULTS: Results from the field-testing study led to the formation of the PMR-Impact Scale (PMR-IS), comprising four domains (symptoms, function, psychological and emotional well-being, and steroid side effects). Construct validity and test-retest reliability met accepted quality-criteria for each domain. There was insufficient evidence from this study to determine its ability to detect flares/deterioration, but the PMR-IS was responsive to improvements in the condition. CONCLUSION: The PMR-IS offers researchers a new way to assess patient-reported outcomes in clinical studies of PMR. It has been developed robustly, with patient input at every stage. It has good construct validity and test re-test reliability. Further work is needed to fully establish its responsiveness and interpretability parameters and assess its real-world clinical utility

Challenges in the diagnosis of leptospirosis outwith endemic settings: a Scottish single centre experience

Background Leptospirosis is a zoonotic infection occurring worldwide but endemic in tropical countries. This study describes diagnostic testing for leptospirosis at our institution in Scotland over a 10-year period. Method We identified patients with blood samples referred to the Public Health England reference laboratory for leptospirosis testing between 2006 and 2016. Results A total of 480 samples were sent for IgM ELISA testing with 26 positive results from 14 patients. Two patients met criteria for ‘confirmed’ leptospirosis (microscopic agglutination test > 1:320 in one case and a positive PCR in the other) and the remaining 12 were ‘probable’ on the basis of IgM ELISA positivity, though 9 did not have microscopic agglutination testing performed. Nine infections were imported, mostly from Asia and with a history of fresh water exposure. Three co-infections (respiratory syncytial virus, influenza B and Campylobacter sp.) were identified. Conclusions Practical issues with microscopic agglutination testing (insufficient blood sent to reference laboratory) and PCR (travellers returning > 7 days after illness onset) represent challenges to the laboratory confirmation of a clinical diagnosis of leptospirosis. Co-infection and infectious/auto-immune causes of false positive serology should be evaluated

Detection of chromosome aberrations in the human interphase nucleus by visualization of specific target DNAs with radioactive and non-radioactive in situ hybridization techniques: diagnosis of trisomy 18 with probe L1.84

The localization of chromosome 18 in human interphase nuclei is demonstrated by use of radioactive and nonradioactive in situ hybridization techniques with a DNA clone designated L1.84. This clone represents a distinct subpopulation of the repetitive human alphoid DNA family, located in the centric region of chromosome 18. Under stringent hybridization conditions hybridization of L1.84 is restricted to chromosome 18 and reflects the number of these chromosomes present in the nuclei, namely, two in normal diploid human cells and three in nuclei from cells with trisomy 18. Under conditions of low stringency, cross-hybridization with other subpopulations of the alphoid DNA family occurs in the centromeric regions of the whole chromosome complement, and numerous hybridization sites are detected over interphase nuclei. Detection of chromosome-specific target DNAs by non-radioactive in situ hybridization with appropriate DNA probes cloned from individual chromosomal subregions presents a rapid means of identifying directly numerical or even structural chromosome aberrations in the interphase nucleus. Present limitations and future applications of interphase cytogenetics are discussed

MTN-001: Randomized Pharmacokinetic Cross-Over Study Comparing Tenofovir Vaginal Gel and Oral Tablets in Vaginal Tissue and Other Compartments

Background: Oral and vaginal preparations of tenofovir as pre-exposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection have demonstrated variable efficacy in men and women prompting assessment of variation in drug concentration as an explanation. Knowledge of tenofovir concentration and its active form, tenofovir diphosphate, at the putative vaginal and rectal site of action and its relationship to concentrations at multiple other anatomic locations may provide key information for both interpreting PrEP study outcomes and planning future PrEP drug development. Objective: MTN-001 was designed to directly compare oral to vaginal steady-state tenofovir pharmacokinetics in blood, vaginal tissue, and vaginal and rectal fluid in a paired cross-over design. Methods and Findings: We enrolled 144 HIV-uninfected women at 4 US and 3 African clinical research sites in an open label, 3-period crossover study of three different daily tenofovir regimens, each for 6 weeks (oral 300 mg tenofovir disoproxil fumarate, vaginal 1% tenofovir gel [40 mg], or both). Serum concentrations after vaginal dosing were 56-fold lower than after oral dosing (p<0.001). Vaginal tissue tenofovir diphosphate was quantifiable in ≥90% of women with vaginal dosing and only 19% of women with oral dosing. Vaginal tissue tenofovir diphosphate was ≥130-fold higher with vaginal compared to oral dosing (p<0.001). Rectal fluid tenofovir concentrations in vaginal dosing periods were higher than concentrations measured in the oral only dosing period (p<0.03). Conclusions: Compared to oral dosing, vaginal dosing achieved much lower serum concentrations and much higher vaginal tissue concentrations. Even allowing for 100-fold concentration differences due to poor adherence or less frequent prescribed dosing, vaginal dosing of tenofovir should provide higher active site concentrations and theoretically greater PrEP efficacy than oral dosing; randomized topical dosing PrEP trials to the contrary indicates that factors beyond tenofovir's antiviral effect substantially influence PrEP efficacy. Trial Registration: ClinicalTrials.gov NCT00592124

Normal levels of p27Xic1 are necessary for somite segmentation and determining pronephric organ size

The Xenopus laevis cyclin dependent kinase inhibitor p27Xic1 has been shown to be involved in exit from the cell cycle and differentiation of cells into a quiescent state in the nervous system, muscle tissue, heart and retina. We show that p27Xic1 is expressed in the developing kidney in the nephrostomal regions. Using over-expression and morpholino oligonucleotide (MO) knock-down approaches we show normal levels of p27Xic1 regulate pronephros organ size by regulating cell cycle exit. Knock-down of p27Xic1 expression using a MO prevented myogenesis, as previously reported; an effect that subsequently inhibits pronephrogenesis. Furthermore, we show that normal levels of p27Xic1 are required for somite segmentation also through its cell cycle control function. Finally, we provide evidence to suggest correct paraxial mesoderm segmentation is not necessary for pronephric induction in the intermediate mesoderm. These results indicate novel developmental roles for p27Xic1, and reveal its differentiation function is not universally utilised in all developing tissues

Building block libraries and structural considerations in the self-assembly of polyoxometalate and polyoxothiometalate systems

Inorganic metal-oxide clusters form a class of compounds that are unique in their topological and electronic versatility and are becoming increasingly more important in a variety of applications. Namely, Polyoxometalates (POMs) have shown an unmatched range of physical properties and the ability to form structures that can bridge several length scales. The formation of these molecular clusters is often ambiguous and is governed by self-assembly processes that limit our ability to rationally design such molecules. However, recent years have shown that by considering new building block principles the design and discovery of novel complex clusters is aiding our understanding of this process. Now with current progress in thiometalate chemistry, specifically polyoxothiometalates (POTM), the field of inorganic molecular clusters has further diversified allowing for the targeted development of molecules with specific functionality. This chapter discusses the main differences between POM and POTM systems and how this affects synthetic methodologies and reactivities. We will illustrate how careful structural considerations can lead to the generation of novel building blocks and further deepen our understanding of complex systems

The scale of population structure in Arabidopsis thaliana

The population structure of an organism reflects its evolutionary history and influences its evolutionary trajectory. It constrains the combination of genetic diversity and reveals patterns of past gene flow. Understanding it is a prerequisite for detecting genomic regions under selection, predicting the effect of population disturbances, or modeling gene flow. This paper examines the detailed global population structure of Arabidopsis thaliana. Using a set of 5,707 plants collected from around the globe and genotyped at 149 SNPs, we show that while A. thaliana as a species self-fertilizes 97% of the time, there is considerable variation among local groups. This level of outcrossing greatly limits observed heterozygosity but is sufficient to generate considerable local haplotypic diversity. We also find that in its native Eurasian range A. thaliana exhibits continuous isolation by distance at every geographic scale without natural breaks corresponding to classical notions of populations. By contrast, in North America, where it exists as an exotic species, A. thaliana exhibits little or no population structure at a continental scale but local isolation by distance that extends hundreds of km. This suggests a pattern for the development of isolation by distance that can establish itself shortly after an organism fills a new habitat range. It also raises questions about the general applicability of many standard population genetics models. Any model based on discrete clusters of interchangeable individuals will be an uneasy fit to organisms like A. thaliana which exhibit continuous isolation by distance on many scales

Earthquake lubrication and healing explained by amorphous nanosilica

During earthquake propagation, geologic faults lose their strength, then strengthen as slip slows and stops. Many slip-weakening mechanisms are active in the upper-mid crust, but healing is not always well-explained. Here we show that the distinct structure and rate-dependent properties of amorphous nanopowder (not silica gel) formed by grinding of quartz can cause extreme strength loss at high slip rates. We propose a weakening and related strengthening mechanism that may act throughout the quartz-bearing continental crust. The action of two slip rate-dependent mechanisms offers a plausible explanation for the observed weakening: thermally-enhanced plasticity, and particulate flow aided by hydrodynamic lubrication. Rapid cooling of the particles causes rapid strengthening, and inter-particle bonds form at longer timescales. The timescales of these two processes correspond to the timescales of post-seismic healing observed in earthquakes. In natural faults, this nanopowder crystallizes to quartz over 10s–100s years, leaving veins which may be indistinguishable from common quartz veins