Preliminary calibration results for the BATSE instrument on CGRO

Preliminary results pertaining to spectral reconstruction using Burst and Transient Source (BATSE) Large Area Detector measurements of solar flares are presented. The solar flare measurements are currently being used to fine tune the calibration of our data analysis software. The current status of the stability of spectral analysis, given the systematic errors present in burst location, are given. A brief description is given of enhancements to the input data for the atmospheric scattering algorithm that will be implemented in the data analysis software

Genome-wide association study identifies 30 loci associated with bipolar disorder.

Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P < 1 × 10-4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (P < 5 × 10-8) in the discovery GWAS were not genome-wide significant in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis, 30 loci were genome-wide significant, including 20 newly identified loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene sets, including regulation of insulin secretion and endocannabinoid signaling. Bipolar I disorder is strongly genetically correlated with schizophrenia, driven by psychosis, whereas bipolar II disorder is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential biological mechanisms for bipolar disorder

Detecting modification of biomedical events using a deep parsing approach

<p>Abstract</p> <p>Background</p> <p>This work describes a system for identifying event mentions in bio-molecular research abstracts that are either speculative (e.g. <it>analysis of IkappaBalpha phosphorylation</it>, where it is not specified whether phosphorylation did or did not occur) or negated (e.g. <it>inhibition of IkappaBalpha phosphorylation</it>, where phosphorylation did <it>not </it>occur). The data comes from a standard dataset created for the BioNLP 2009 Shared Task. The system uses a machine-learning approach, where the features used for classification are a combination of shallow features derived from the words of the sentences and more complex features based on the semantic outputs produced by a deep parser.</p> <p>Method</p> <p>To detect event modification, we use a Maximum Entropy learner with features extracted from the data relative to the trigger words of the events. The shallow features are bag-of-words features based on a small sliding context window of 3-4 tokens on either side of the trigger word. The deep parser features are derived from parses produced by the English Resource Grammar and the <it>RASP </it>parser. The outputs of these parsers are converted into the Minimal Recursion Semantics formalism, and from this, we extract features motivated by linguistics and the data itself. All of these features are combined to create training or test data for the machine learning algorithm.</p> <p>Results</p> <p>Over the test data, our methods produce approximately a 4% absolute increase in F-score for detection of event modification compared to a baseline based only on the shallow bag-of-words features.</p> <p>Conclusions</p> <p>Our results indicate that grammar-based techniques can enhance the accuracy of methods for detecting event modification.</p

Photosensitizer Drug Delivery via an Optical Fiber

: An optical fiber has been developed with a maneuverable miniprobe tip that sparges O2 gas and photodetaches pheophorbide (sensitizer) molecules. Singlet oxygen is produced at the probe tip surface which reacts with an alkene spacer group releasing sensitizer upon fragmentation of a dioxetane intermediate. Optimal sensitizer photorelease occurred when the probe tip was loaded with 60 nmol sensitizer, where crowding of the pheophorbide molecules and self-quenching were kept to a minimum. The fiber optic tip delivered pheophorbide molecules and singlet oxygen to discrete locations. The 60 nmol sensitizer was delivered into petrolatum; however, sensitizer release was less efficient in toluene-d8 (3.6 nmol) where most had remained adsorbed on the probe tip, even after the covalent alkene spacer bond had been broken. The results open the door to a new area of fiber optic-guided sensitizer delivery for the potential photodynamic therapy of hypoxic structures requiring cytotoxic control

On the contact detection for contact-impact analysis in multibody systems

One of the most important and complex parts of the simulation of multibody systems with contact-impact involves the detection of the precise instant of impact. In general, the periods of contact are very small and, therefore, the selection of the time step for the integration of the time derivatives of the state variables plays a crucial role in the dynamics of multibody systems. The conservative approach is to use very small time steps throughout the analysis. However, this solution is not efficient from the computational view point. When variable time step integration algorithms are used and the pre-impact dynamics does not involve high-frequencies the integration algorithms may use larger time steps and the contact between two surfaces may start with initial penetrations that are artificially high. This fact leads either to a stall of the integration algorithm or to contact forces that are physically impossible which, in turn, lead to post-impact dynamics that is unrelated to the physical problem. The main purpose of this work is to present a general and comprehensive approach to automatically adjust the time step, in variable time step integration algorithms, in the vicinity of contact of multibody systems. The proposed methodology ensures that for any impact in a multibody system the time step of the integration is such that any initial penetration is below any prescribed threshold. In the case of the start of contact, and after a time step is complete, the numerical error control of the selected integration algorithm is forced to handle the physical criteria to accept/reject time steps in equal terms with the numerical error control that it normally uses. The main features of this approach are the simplicity of its computational implementation, its good computational efficiency and its ability to deal with the transitions between non contact and contact situations in multibody dynamics. A demonstration case provides the results that support the discussion and show the validity of the proposed methodology.Fundação para a Ciência e a Tecnologia (FCT

Identification of calcium-binding proteins associated with the human sperm plasma membrane

<p>Abstract</p> <p>Background</p> <p>The precise composition of the human sperm plasma membrane, the molecular interactions that define domain specific functions, and the regulation of membrane associated proteins during the capacitation process, still remain to be fully understood. Here, we investigated the repertoire of calcium-regulated proteins associated with the human sperm plasma membrane.</p> <p>Methods</p> <p>Surface specific radioiodination was combined with two-dimensional gel electrophoresis, a 45Ca-overlay assay, computer assisted image analysis and mass spectrometry to identify calcium-binding proteins exposed on the human sperm surface.</p> <p>Results</p> <p>Nine acidic 45Ca-binding sperm proteins were excised from stained preparative 2D gels and identified by mass spectrometry. Five of the calcium binding proteins; HSPA2 (HSP70-1), HSPA5 (Bip), HYOU1 (ORP150), serum amyloid P-component (SAP) and protein kinase C substrate 80K-H (80K-H) were found to be accessible to Iodo-Bead catalyzed 125I-labelling on the surface of intact human sperm. Agglutination and immunofluorescence analysis confirmed that SAP is situated on the plasma membrane of intact, motile sperm as well as permeabilized cells. Western blot analysis showed increased phosphorylation of human sperm 80K-H protein following in vitro capacitation. This is the first demonstration of the 80K-H protein in a mammalian sperm.</p> <p>Conclusion</p> <p>The presence of SAP on the surface of mature sperm implies that SAP has a physiological role in reproduction, which is thought to be in the removal of spermatozoa from the female genital tract via phagocytosis. Since 80K-H is a Ca2+-sensor recently implicated in the regulation of both inositol 1,4,5-trisphosphate receptor and transient receptor potential (TRP) cation channel activities, its detection in sperm represents the first direct signaling link between PKC and store-operated calcium channels identified in human sperm.</p

Radiotherapeutic alternatives for previously irradiated recurrent gliomas

Re-irradiation for recurrent gliomas has been discussed controversially in the past. This was mainly due to only marginal palliation while being associated with a high risk for side effects using conventional radiotherapy

The role of whole brain radiation therapy in the management of newly diagnosed brain metastases: a systematic review and evidence-based clinical practice guideline

QUESTION: Should patients with newly-diagnosed metastatic brain tumors undergo open surgical resection versus whole brain radiation therapy (WBRT) and/or other treatment modalities such as radiosurgery, and in what clinical settings? TARGET POPULATION: These recommendations apply to adults with a newly diagnosed single brain metastasis amenable to surgical resection. RECOMMENDATIONS: Surgical resection plus WBRT versus surgical resection alone Level 1 Surgical resection followed by WBRT represents a superior treatment modality, in terms of improving tumor control at the original site of the metastasis and in the brain overall, when compared to surgical resection alone. Surgical resection plus WBRT versus SRS + or - WBRT Level 2 Surgical resection plus WBRT, versus stereotactic radiosurgery (SRS) plus WBRT, both represent effective treatment strategies, resulting in relatively equal survival rates. SRS has not been assessed from an evidence-based standpoint for larger lesions (\u3e3 cm) or for those causing significant mass effect (\u3e1 cm midline shift). Level 3 Underpowered class I evidence along with the preponderance of conflicting class II evidence suggests that SRS alone may provide equivalent functional and survival outcomes compared with resection + WBRT for patients with single brain metastases, so long as ready detection of distant site failure and salvage SRS are possible. Note The following question is fully addressed in the WBRT guideline paper within this series by Gaspar et al. Given that the recommendation resulting from the systematic review of the literature on this topic is also highly relevant to the discussion of the role of surgical resection in the management of brain metastases, this recommendation has been included below