A critical review of PASBio's argument structures for biomedical verbs

BACKGROUND: Propositional representations of biomedical knowledge are a critical component of most aspects of semantic mining in biomedicine. However, the proper set of propositions has yet to be determined. Recently, the PASBio project proposed a set of propositions and argument structures for biomedical verbs. This initial set of representations presents an opportunity for evaluating the suitability of predicate-argument structures as a scheme for representing verbal semantics in the biomedical domain. Here, we quantitatively evaluate several dimensions of the initial PASBio propositional structure repository. RESULTS: We propose a number of metrics and heuristics related to arity, role labelling, argument realization, and corpus coverage for evaluating large-scale predicate-argument structure proposals. We evaluate the metrics and heuristics by applying them to PASBio 1.0. CONCLUSION: PASBio demonstrates the suitability of predicate-argument structures for representing aspects of the semantics of biomedical verbs. Metrics related to theta-criterion violations and to the distribution of arguments are able to detect flaws in semantic representations, given a set of predicate-argument structures and a relatively small corpus annotated with them

Spin dynamics of molecular nanomagnets fully unraveled by four-dimensional inelastic neutron scattering

Molecular nanomagnets are among the first examples of spin systems of finite size and have been test-beds for addressing a range of elusive but important phenomena in quantum dynamics. In fact, for short-enough timescales the spin wavefunctions evolve coherently according to the an appropriate cluster spin-Hamiltonian, whose structure can be tailored at the synthetic level to meet specific requirements. Unfortunately, to this point it has been impossible to determine the spin dynamics directly. If the molecule is sufficiently simple, the spin motion can be indirectly assessed by an approximate model Hamiltonian fitted to experimental measurements of various types. Here we show that recently-developed instrumentation yields the four-dimensional inelastic-neutron scattering function S(Q,E) in vast portions of reciprocal space and enables the spin dynamics to be determined with no need of any model Hamiltonian. We exploit the Cr8 antiferromagnetic ring as a benchmark to demonstrate the potential of this new approach. For the first time we extract a model-free picture of the quantum dynamics of a molecular nanomagnet. This allows us, for example, to examine how a quantum fluctuation propagates along the ring and to directly test the degree of validity of the N\'{e}el-vector-tunneling description of the spin dynamics

The effect of Ku on telomere replication time is mediated by telomere length but is independent of histone tail acetylation

Peer reviewedPublisher PD

Optic Nerve Head Quantification in Idiopathic Intracranial Hypertension by Spectral Domain OCT

Objective: To evaluate 3D spectral domain optical coherence tomography (SDOCT) volume scans as a tool for quantification of optic nerve head (ONH) volume as a potential marker for treatment effectiveness and disease progression in idiopathic intracranial hypertension (IIH). Design and Patients: Cross-sectional pilot trial comparing 19 IIH patients and controls matched for gender, age and body mass index. Each participant underwent SDOCT. A custom segmentation algorithm was developed to quantify ONH volume (ONHV) and height (ONHH) in 3D volume scans. Results:Whereas peripapillary retinal nerve fiber layer thickness did not show differences between controls and IIH patients, the newly developed 3D parameters ONHV and ONHH were able to discriminate between controls, treated and untreated patients. Both ONHV and ONHH measures were related to levels of intracranial pressure (ICP). Conclusion: Our findings suggest 3D ONH measures as assessed by SDOCT as potential diagnostic and progression markers in IIH and other disorders with increased ICP. SDOCT may promise a fast and easy diagnostic alternative to repeated lumba

Mediastinal lymph node metastasis model by orthotopic intrapulmonary implantation of Lewis lung carcinoma cells in mice

This study is designed to establish a pulmonary tumour model to investigate the biology and therapy of lung cancer in mice. Current methods for forming a solitary intrapulmonary nodule and subsequent metastasis to mediastinal lymph nodes are not well defined. Lewis lung carcinoma (LLC) cell suspensions were orthotopically introduced into the lung parenchyma of C57/BL6 mice via a limited skin incision without thoracotomy followed by direct puncture through the intercostal space. The implantation process was performed within approximately 50 s per mouse, and the operative mortality was less than 5%. Single pulmonary nodules developed at the implanted site in 93% of animals and subsequent mediastinal lymph node metastasis was observed in all mice that formed a lung nodule after intrapulmonary implantation. The size of tumour nodule and the weight of mediastinal lymph node increased in a time-dependent manner. The mean survival time of mice implanted successfully with LLC cells was 21 ± 2 days (range 19–24 days). Histopathological analysis revealed that no metastatic tumour was detectable in the mediastinal lymph nodes on day 11, but metastatic foci at mediastinal lymph nodes were clearly observed on days 17 and 21 after implantation. Other metastases in distant organs or lymph nodes were not observed at 21 days after the implantation. Comparative studies with intrapleural and intravenous injections of LLC cells suggest that the mediastinal lymph node metastasis by intrapulmonary impantation is due to the release of tumour cells from the primary nodule, and not due to extrapulmonary leakage of cells. An intravenous administration of cis-diamine dichrolo platinum on day 1 after tumour implantation tended to suppress the primary tumour nodule and significantly inhibited lymph node metastasis. Thus, a solitary pulmonary tumour nodule model with lymph node metastasis approximates clinical lung cancer and may provide a useful basis for lung cancer research. © 1999 Cancer Research Campaig

Evolutionary approaches for the reverse-engineering of gene regulatory networks: A study on a biologically realistic dataset

<p>Abstract</p> <p>Background</p> <p>Inferring gene regulatory networks from data requires the development of algorithms devoted to structure extraction. When only static data are available, gene interactions may be modelled by a Bayesian Network (BN) that represents the presence of direct interactions from regulators to regulees by conditional probability distributions. We used enhanced evolutionary algorithms to stochastically evolve a set of candidate BN structures and found the model that best fits data without prior knowledge.</p> <p>Results</p> <p>We proposed various evolutionary strategies suitable for the task and tested our choices using simulated data drawn from a given bio-realistic network of 35 nodes, the so-called insulin network, which has been used in the literature for benchmarking. We assessed the inferred models against this reference to obtain statistical performance results. We then compared performances of evolutionary algorithms using two kinds of recombination operators that operate at different scales in the graphs. We introduced a niching strategy that reinforces diversity through the population and avoided trapping of the algorithm in one local minimum in the early steps of learning. We show the limited effect of the mutation operator when niching is applied. Finally, we compared our best evolutionary approach with various well known learning algorithms (MCMC, K2, greedy search, TPDA, MMHC) devoted to BN structure learning.</p> <p>Conclusion</p> <p>We studied the behaviour of an evolutionary approach enhanced by niching for the learning of gene regulatory networks with BN. We show that this approach outperforms classical structure learning methods in elucidating the original model. These results were obtained for the learning of a bio-realistic network and, more importantly, on various small datasets. This is a suitable approach for learning transcriptional regulatory networks from real datasets without prior knowledge.</p

Maternal hypoxia decreases capillary supply and increases metabolic inefficiency leading to divergence in myocardial oxygen supply and demand

Maternal hypoxia is associated with a decrease in left ventricular capillary density while cardiac performance is preserved, implying a mismatch between metabolism and diffusive exchange. We hypothesised this requires a switch in substrate metabolism to maximise efficiency of ATP production from limited oxygen availability. Rat pups from pregnant females exposed to hypoxia (FIO2=0.12) at days 10-20 of pregnancy were grown to adulthood and working hearts perfused ex vivo. 14 C-labelled glucose and 3 H-palmitate were provided as substrates and metabolism quantified from recovery of 14CO2 and 3 H2O, respectively. Hearts of male offspring subjected to Maternal Hypoxia showed a 20% decrease in cardiac output (P<0.05), despite recording a 2-fold increase in glucose oxidation (P<0.01) and 2.5-fold increase (P<0.01) in palmitate oxidation. Addition of insulin to Maternal Hypoxic hearts, further increased glucose oxidation (P<0.01) and suppressed palmitate oxidation (P<0.05), suggesting preservation in insulin signalling in the heart. In vitro enzyme activity measurements showed that Maternal Hypoxia increased both total and the active component of cardiac pyruvate dehydrogenase (both P<0.01), although pyruvate dehydrogenase sensitivity to insulin was lost (NS), while citrate synthase activity declined by 30% (P<0.001) and acetyl-CoA carboxylase activity was unchanged by Maternal Hypoxia, indicating realignment of the metabolic machinery to optimise oxygen utilisation. Capillary density was quantified and oxygen diffusion characteristics examined, with calculated capillary domain area increased by 30% (P<0.001). Calculated metabolic efficiency decreased 4-fold (P<0.01) for Maternal Hypoxia hearts. Paradoxically, the decline in citrate synthase activity and increased metabolism suggest that the scope of individual mitochondria had declined, rendering the myocardium potentially more sensitive to metabolic stress. However, decreasing citrate synthase may be essential to preserve local PO2, minimising regions of hypoxia and hence maximising the area of myocardium able to preserve cardiac output following maternal hypoxia