Maternally supplied S-acyl-transferase is required for crystalloid organelle formation and transmission of the malaria parasite.

Transmission of the malaria parasite from the mammalian host to the mosquito vector requires the formation of adequately adapted parasite forms and stage-specific organelles. Here we show that formation of the crystalloid-a unique and short-lived organelle of the Plasmodium ookinete and oocyst stage required for sporogony-is dependent on the precisely timed expression of the S-acyl-transferase DHHC10. DHHC10, translationally repressed in female Plasmodium berghei gametocytes, is activated translationally during ookinete formation, where the protein is essential for the formation of the crystalloid, the correct targeting of crystalloid-resident protein LAP2, and malaria parasite transmission

Structural identification and biological activity of 7-methyl-10,11-ethylenedioxy-20(S)-camptothecin, a photodegradant of lurtotecan

An additional chromatographic peak was observed in plasma samples of patients receiving NX 211, a liposomal formulation of the topoisomerase I inhibitor lurtotecan. We have isolated and purified this product by sequential solid-phase extractions, and we report its structure and cytotoxicity relative to lurtotecan and related agents. Nuclear magnetic resonance data indicate that cleavage of the piperazino moiety occurred at the N-C bond of the B-ring, yielding 7-methyl-10,11-ethylenedioxy-20(S)-camptothecin (MEC). Tests of the growth inhibition potential of MEC in seven human tumor cell lines showed that the compound was approximately 2-18-fold more cytotoxic than lurtotecan, topotecan, and 7-ethyl-10-hydroxy-20(S)-camptothecin (SN-38). Subsequently, we found that MEC was the product of rapid photolysis of lurtotecan, with the rate of degradation inversely proportional to NX 211 concentrations, and greatly depends on light intensity. Furthermore, MEC concentrations were found to increase significantly in plasma samples exposed to laboratory light but not in blood. MEC was not produced from NX 211 in the presence of human liver microsomes, suggesting that it is not a product of cytochrome P-450 metabolism. Using a validated analytical method, trace levels of MEC were quantitated in blood samples of two patients. These observations confirm that the precautions for protection from light currently specified for preparation and administration of NX 211 dose solutions are critical. Procedures to minimize formation of MEC, by the use of amber vials for NX 211 and by preparation of dilutions immediately before clinical use in a fashion completely protected from light, are now being routinely implemented

On the challenges and opportunities in visualization for machine learning and knowledge extraction: A research agenda

We describe a selection of challenges at the intersection of machine learning and data visualization and outline a subjective research agenda based on professional and personal experience. The unprecedented increase in the amount, variety and the value of data has been significantly transforming the way that scientific research is carried out and businesses operate. Within data science, which has emerged as a practice to enable this data-intensive innovation by gathering together and advancing the knowledge from fields such as statistics, machine learning, knowledge extraction, data management, and visualization, visualization plays a unique and maybe the ultimate role as an approach to facilitate the human and computer cooperation, and to particularly enable the analysis of diverse and heterogeneous data using complex computational methods where algorithmic results are challenging to interpret and operationalize. Whilst algorithm development is surely at the center of the whole pipeline in disciplines such as Machine Learning and Knowledge Discovery, it is visualization which ultimately makes the results accessible to the end user. Visualization thus can be seen as a mapping from arbitrarily high-dimensional abstract spaces to the lower dimensions and plays a central and critical role in interacting with machine learning algorithms, and particularly in interactive machine learning (iML) with including the human-in-the-loop. The central goal of the CD-MAKE VIS workshop is to spark discussions at this intersection of visualization, machine learning and knowledge discovery and bring together experts from these disciplines. This paper discusses a perspective on the challenges and opportunities in this integration of these discipline and presents a number of directions and strategies for further research

SVA retrotransposon insertion-associated deletion represents a novel mutational mechanism underlying large genomic copy number changes with non-recurrent breakpoints

Background: Genomic disorders are caused by copy number changes that may exhibit recurrent breakpoints processed by nonallelic homologous recombination. However, region-specific disease-associated copy number changes have also been observed which exhibit non-recurrent breakpoints. The mechanisms underlying these non-recurrent copy number changes have not yet been fully elucidated. Results: We analyze large NF1 deletions with non-recurrent breakpoints as a model to investigate the full spectrum of causative mechanisms, and observe that the

Extensive Copy-Number Variation of Young Genes across Stickleback Populations

MM received funding from the Max Planck innovation funds for this project. PGDF was supported by a Marie Curie European Reintegration Grant (proposal nr 270891). CE was supported by German Science Foundation grants (DFG, EI 841/4-1 and EI 841/6-1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Steady operation of the electric drive of pipeline armature in the emergency situation at low ambient temperatures

This scientific work is devoted to the study of the electric drive operation of pipeline armature at low ambient temperatures. Hit of moisture into reducer and rare inclusions in operation of locking regulator are led to curdling lubricant that causes the increased wear of mechanical knots. There is a probability of freezing mechanical components; it leads to emergency situations. The problem of improving working efficiency of the electric drive of shut-off regulating armature at low ambient temperatures of the environment is solved in this work. A simulation model of the GUSAR electric drive was developed to solve this problem. Studies of the simulation model show the need to limit the torque increase rate on a drive motor shaft. The algorithm of setting of PI speed controller to obtain acceptable transient processes is suggested. Recommendations for the use of the algorithm in the microprocessor control system of electric drive are proposed. It is shown that the electric drive operation algorithm with torque increasing limitation on the motor shaft will be smoothly working off the perturbing actions that occur in pipeline armature

Rapid and Precise Semi-Automatic Axon Quantification in Human Peripheral Nerves

We developed a time-efficient semi-automated axon quantification method using freeware in human cranial nerve sections stained with paraphenylenediamine (PPD). It was used to analyze a total of 1238 facial and masseteric nerve biopsies. The technique was validated by comparing manual and semi-automated quantification of 129 (10.4%) randomly selected biopsies. The software-based method demonstrated a sensitivity of 94% and a specificity of 87%. Semi-automatic axon counting was significantly faster (p<0.001) than manual counting. It took 1hour and 47minutes for all 129 biopsies (averaging 50sec per biopsy, 0.04seconds per axon). The counting process is automatic and does not need to be supervised. Manual counting took 21hours and 6minutes in total (average 9minutes and 49seconds per biopsy, 0.52seconds per axon). Our method showed a linear correlation to the manual counts (R=0.944 Spearman rho). Attempts have been made by several research groups to automate axonal load quantification. These methods often require specific hard- and software and are therefore only accessible to a few specialized laboratories. Our semi-automated axon quantification is precise, reliable and time-sparing using publicly available software and should be useful for an effective axon quantification in various human peripheral nerves