Bio-SCoRes: A Smorgasbord Architecture for Coreference Resolution in Biomedical Text

Coreference resolution is one of the fundamental and challenging tasks in natural language processing. Resolving coreference successfully can have a significant positive effect on downstream natural language processing tasks, such as information extraction and question answering. The importance of coreference resolution for biomedical text analysis applications has increasingly been acknowledged. One of the difficulties in coreference resolution stems from the fact that distinct types of coreference (e.g., anaphora, appositive) are expressed with a variety of lexical and syntactic means (e.g., personal pronouns, definite noun phrases), and that resolution of each combination often requires a different approach. In the biomedical domain, it is common for coreference annotation and resolution efforts to focus on specific subcategories of coreference deemed important for the downstream task. In the current work, we aim to address some of these concerns regarding coreference resolution in biomedical text. We propose a general, modular framework underpinned by a smorgasbord architecture (Bio-SCoRes), which incorporates a variety of coreference types, their mentions and allows fine-grained specification of resolution strategies to resolve coreference of distinct coreference type-mention pairs. For development and evaluation, we used a corpus of structured drug labels annotated with fine-grained coreference information. In addition, we evaluated our approach on two other corpora (i2b2/VA discharge summaries and protein coreference dataset) to investigate its generality and ease of adaptation to other biomedical text types. Our results demonstrate the usefulness of our novel smorgasbord architecture. The specific pipelines based on the architecture perform successfully in linking coreferential mention pairs, while we find that recognition of full mention clusters is more challenging. The corpus of structured drug labels (SPL) as well as the components of Bio-SCoRes and some of the pipelines based on it are publicly available at https://github.com/kilicogluh/Bio-SCoRes. We believe that Bio-SCoRes can serve as a strong and extensible baseline system for coreference resolution of biomedical text.     

The effect of Na+-K+ ATPase inhibition by ouabain on histamine release from human cutaneous mast cells

Background: There are controversial reports on the effect of sodium-potassium adenosine triphosphatase (Na⁺-K⁺ ATPase) inhibition on mast cell mediator release. Some of them have indicated that ouabain (strophanthin G), a specific Na⁺-K⁺ ATPase inhibitor, inhibited the release, whereas the others have shown that ouabain had no effect or even had a stimulatory effect on the mediator secretion. Most of these studies have utilized animal-derived mast cells. The aim of this study was to determine the effect of Na⁺-K⁺ ATPase inhibition on human skin mast cells. Methods: Unpurified and purified mast cells were obtained from newborn foreskins and stimulated by calcium ionophore A23187 (1 μM) for 30 min following a 1 hr incubation with various concentrations (10⁻⁴ to 10⁻⁸ M) of ouabain. Histamine release was assayed by enzyme-linked immunosorbent assay (ELISA). Results: The results indicated that ouabain had no significant effect on the non-immunologic histamine release from human skin mast cells, in vitro. Conclusions: Na⁺-K⁺ ATPase inhibition by ouabain had no significant effect on the non-immunologic histamine release from human cutaneous mast cells and suggested differences between human and animal mast cells.     

A novel proton transfer salt of 2-amino-6-sulfamoylbenzothiazole and its metal complexes: the evaluation of their inhibition effects on human cytosolic carbonic anhydrases

A novel proton transfer compound (SMHABT)⁺(HDPC)^? (1) obtained from 2-amino-6-sulfamoylbenzothiazole (SMABT) and 2,6-pyridinedicarboxylic acid (H₂DPC) and its Fe(III), Co(II), Ni(II) complexes (2–4), and Fe(II) complex of SMABT (5) have been prepared and characterized by spectroscopic techniques. Additionally, single crystal X-ray diffraction techniques were applied to complexes (2–4). All complexes (2–4) have distorted octahedral conformations and the structure of 5 might be proposed as octahedral according to spectral and analytical results. All compounds, including acetazolamide (AAZ) as the control compound, were also evaluated for their in vitro inhibition effects on human hCA I and hCA II for their hydratase and esterase activities. The synthesized compounds have remarkable inhibitory activities on hCA I and hCA II. Especially, the inhibition potentials of the salt and the metal complexes (1–5) are comparable with AAZ. Inhibition data have been analyzed by using a one-way analysis of variance for multiple comparisons (p?相似文献   

Protective effect of alpha-linolenic acid on gentamicin-induced ototoxicity in mice

Alpha-linolenic acid is one of the fatty acids known as omega 3. Previous studies have shown the antioxidant and anti-inflammatory effects of alpha-linolenic acid, which prevented cell damage by inhibiting apoptotic pathway. Also, it is known that gentamicin activates apoptotic mediators and causes necrosis in the kidney. Due to this reason, we planned a study to evaluate the protective effects of alpha-linolenic acid on gentamicin induced ototoxicity by evaluating inflammation and apoptotic mediators. For this purpose, 100?mg/kg gentamicin (i.p; intraperitoneally) and 200?mg/kg alpha-linolenic acid (gavage) are administered to mice for 9?days. On 9th and 10th days, rotarod performance was assessed to test the effect of gentamicin and alpha-linolenic acid treatment on the motor coordination of mice. Gentamicin treatment decreased fall latency of mice and gentamicin treatment together with alpha-linolenic acid increased fall latency of mice. Gentamicin treatment also increased expression of phospholipase A2(plA2), cyclooxygenase-2(COX-2) and inducible nitric oxide syntheses (iNOS). Furthermore, it increased Bax and caspase-3, which are proapoptotic proteins and decreased bcl-2 that is an antiapoptotic protein. Gentamicin treatment together alpha-linolenic acid recovered the change of expression of these enzymes. In conclusion, this study showed that alpha-linolenic acid will be useful to prevent gentamicin-induced ototoxicity by inhibiting apoptosis and inflammation.     

Plant responses to simulated warming and drought: a comparative study of functional plasticity between congeneric mid and high elevation species

Aims Effects of climate change, especially changes in temperatures and precipitation patterns, are particularly pronounced in alpine regions. In response, plants may exhibit phenotypic plasticity in key functional traits allowing short-term adjustment to novel conditions. However, little is known about the degree of phenotypic plasticity of high elevation species relative to mid elevation congeners.Methods We transplanted 14 herbaceous perennial species from high elevation into two common gardens (1050 and 2000 m.a.s.l.) in the Swiss Alps, and we examined plastic responses in key functional traits to changes in temperature and soil water availability. This design was replicated with 14 congeneric species from mid elevation to assess if the degree of phenotypic plasticity differs between mid and high elevation species. Survival was assessed across two growing seasons, while aboveground biomass and specific leaf area (SLA) were measured after the first growing season, and biomass allocation to belowground and reproductive structures after the second. Moreover, a phenotypic plasticity index was calculated for the functional traits to compare the degree of plasticity between mid and high elevation species.Important findings Aboveground biomass was higher in mid elevation species relative to high elevation congeners in all treatments, yet decreased for both with elevation and drought. Similarly, SLA decreased with elevation and drought. Root mass fraction (RMF) was generally higher in high elevation species, and decreased with drought at the lower site. Drought increased the allocation to reproductive structures, especially when plants were grown at their elevation of origin. Interestingly, no difference was found in the degree of phenotypic plasticity averaged across mid and high elevation species for any of the studied functional traits. These results indicate that phenotypic plasticity in the focal traits did not depend on the elevation of origin of the species. Plasticity was not related to environmental heterogeneity, nor constrained by selective pressures at high elevation. However, both species groups showed a remarkable capacity for short-term acclimation to a prospective climate through rapid adjustments in key functional traits.     

Prevalence of Obesity and Associated Risk Factors in a Turkish Population (Trabzon City,Turkey)

Objective: To estimate the prevalence of overweight and obesity (general and central) in the Trabzon Region and its associations with demographic factors (age, sex, marital status, reproductive history in women, and level of education), socioeconomic factors (household income and occupation), family history of selected medical conditions (diabetes, hypertension, and obesity), lifestyle factors (smoking habits, physical activity, and alcohol consumption), and hypertension in the adult population. Research Methods and Procedures: A sample of households was systematically selected from the central province of Trabzon and its five towns, namely, Sürmene, Vakfikebir, Maçka, Hayrat, and Tonya. A total of 5016 subjects (2728 women and 2288 men) were included in the study. Individuals more than 20 years old were selected from their family health cards. Demographic factors, socioeconomic factors, family history of selected medical conditions, and lifestyle factors were obtained for all participants. Systolic blood pressure and diastolic blood pressure levels were measured for all subjects. Study procedures were carried out in the local health centers in each town over an 8‐month period. Obesity was defined as BMI ≥ 30 kg/m² and overweight as BMI = 25.0 to 29.9 kg/m². Results: The prevalence of obesity was 23.5%: 29.4% in women and 16.5% in men. The combined prevalence of both overweight and obesity was 60.3%. The prevalence of abdominal obesity was 29.4%: 38.9% among women and 18.1% among men. The prevalence of obesity increased with age, being highest in the 60‐ to 69‐year‐old age group (40.8%) but lower again in the 70+ age group. Obesity was associated positively with marital status, parity, cessation of cigarette smoking, alcohol consumption, and household income and inversely with level of education, cigarette use, and physical activity. Also, obesity was associated positively with hypertension. Discussion: In the Trabzon Region, 60.3% of the adult population presents with some excess weight. Obesity is a major public health problem that requires generalized interventions to prevent it among the adult population.     

Computational and experimental investigation of DNA repair protein photolyase interactions with low molecular weight drugs

This paper reports the previously unknown interactions between eight low molecular weight commercially available drugs (130–800 Da) and DNA repair protein photolyase using computational docking simulations and surface plasmon resonance (SPR) experiments. Theoretical dissociation constants, K_d, obtained from molecular docking simulations were compared with the values found from SPR experiments. Among the eight drugs analyzed, computational and experimental values showed similar binding affinities between selected drug and protein pairs. We found no significant differences in binding interactions between pure and commercial forms of the drug lornoxicam and DNA photolyase. Among the eight drugs studied, prednisone, desloratadine, and azelastine exhibited the highest binding affinity (K_d = 1.65, 2.05, and 8.47 μM, respectively) toward DNA photolyase. Results obtained in this study are promising for use in the prediction of unknown interactions of common drugs with specific proteins such as human clock protein cryptochrome. Copyright © 2013 John Wiley & Sons, Ltd.     

Investigation of the Interaction between the Large and Small Subunits of Potato ADP-Glucose Pyrophosphorylase

ADP-glucose pyrophosphorylase (AGPase), a key allosteric enzyme involved in higher plant starch biosynthesis, is composed of pairs of large (LS) and small subunits (SS). Current evidence indicates that the two subunit types play distinct roles in enzyme function. Recently the heterotetrameric structure of potato AGPase has been modeled. In the current study, we have applied the molecular mechanics generalized born surface area (MM-GBSA) method and identified critical amino acids of the potato AGPase LS and SS subunits that interact with each other during the native heterotetrameric structure formation. We have further shown the role of the LS amino acids in subunit-subunit interaction by yeast two-hybrid, bacterial complementation assay and native gel. Comparison of the computational results with the experiments has indicated that the backbone energy contribution (rather than the side chain energies) of the interface residues is more important in identifying critical residues. We have found that lateral interaction of the LS-SS is much stronger than the longitudinal one, and it is mainly mediated by hydrophobic interactions. This study will not only enhance our understanding of the interaction between the SS and the LS of AGPase, but will also enable us to engineer proteins to obtain better assembled variants of AGPase which can be used for the improvement of plant yield.