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

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

PPS, a Large Multidomain Protein, Functions with Sex-Lethal to Regulate Alternative Splicing in Drosophila

Alternative splicing controls the expression of many genes, including the Drosophila sex determination gene Sex-lethal (Sxl). Sxl expression is controlled via a negative regulatory mechanism where inclusion of the translation-terminating male exon is blocked in females. Previous studies have shown that the mechanism leading to exon skipping is autoregulatory and requires the SXL protein to antagonize exon inclusion by interacting with core spliceosomal proteins, including the U1 snRNP protein Sans-fille (SNF). In studies begun by screening for proteins that interact with SNF, we identified PPS, a previously uncharacterized protein, as a novel component of the machinery required for Sxl male exon skipping. PPS encodes a large protein with four signature motifs, PHD, BRK, TFS2M, and SPOC, typically found in proteins involved in transcription. We demonstrate that PPS has a direct role in Sxl male exon skipping by showing first that loss of function mutations have phenotypes indicative of Sxl misregulation and second that the PPS protein forms a complex with SXL and the unspliced Sxl RNA. In addition, we mapped the recruitment of PPS, SXL, and SNF along the Sxl gene using chromatin immunoprecipitation (ChIP), which revealed that, like many other splicing factors, these proteins bind their RNA targets while in close proximity to the DNA. Interestingly, while SNF and SXL are specifically recruited to their predicted binding sites, PPS has a distinct pattern of accumulation along the Sxl gene, associating with a region that includes, but is not limited to, the SxlPm promoter. Together, these data indicate that PPS is different from other splicing factors involved in male-exon skipping and suggest, for the first time, a functional link between transcription and SXL–mediated alternative splicing. Loss of zygotic PPS function, however, is lethal to both sexes, indicating that its role may be of broad significance