Do the Results of Divine Actions Have Preceding Causes?

If God brings about an event in the universe, does it have a preceding cause? For example, if the universe began with the Big Bang and if God brought it about, did the Big Bang then have a preceding cause? The standard answer is: yes, it was caused by a divine willing. I propose an alternative view: God’s actions, unlike human actions, are not initiated by willings, undertakings, or volitions, but God brings about the intended event directly. Presenting a solution to the dilemma of free will I explain what ‘bringing about directly’ means and show that the question of what an action begins with is distinct from the question whether it is a basic action

Higher-Order, Data-Parallel Structured Deduction

State-of-the-art Datalog engines include expressive features such as ADTs (structured heap values), stratified aggregation and negation, various primitive operations, and the opportunity for further extension using FFIs. Current parallelization approaches for state-of-art Datalogs target shared-memory locking data-structures using conventional multi-threading, or use the map-reduce model for distributed computing. Furthermore, current state-of-art approaches cannot scale to formal systems which pervasively manipulate structured data due to their lack of indexing for structured data stored in the heap. In this paper, we describe a new approach to data-parallel structured deduction that involves a key semantic extension of Datalog to permit first-class facts and higher-order relations via defunctionalization, an implementation approach that enables parallelism uniformly both across sets of disjoint facts and over individual facts with nested structure. We detail a core language, $DL_s$, whose key invariant (subfact closure) ensures that each subfact is materialized as a top-class fact. We extend $DL_s$ to Slog, a fully-featured language whose forms facilitate leveraging subfact closure to rapidly implement expressive, high-performance formal systems. We demonstrate Slog by building a family of control-flow analyses from abstract machines, systematically, along with several implementations of classical type systems (such as STLC and LF). We performed experiments on EC2, Azure, and ALCF's Theta at up to 1000 threads, showing orders-of-magnitude scalability improvements versus competing state-of-art systems

On Fast Large-Scale Program Analysis in Datalog

Designing and crafting a static program analysis is challenging due to the complexity of the task at hand. Among the challenges are modelling the semantics of the input language, finding suitable abstractions for the analysis, and handwriting efficient code for the analysis in a traditional imperative language such as C++. Hence, the development of static program analysis tools is costly in terms of development time and resources for real world languages. To overcome, or at least alleviate the costs of developing a static program analysis, Datalog has been proposed as a domain specific language (DSL).With Datalog, a designer expresses a static program analysis in the form of a logical specification. While a domain specific language approach aids in the ease of development of program analyses, it is commonly accepted that such an approach has worse runtime performance than handcrafted static analysis tools. In this work, we introduce a new program synthesis methodology for Datalog specifications to produce highly efficient monolithic C++ analyzers. The synthesis technique requires the re-interpretation of the semi-naïve evaluation as a scaffolding for translation using partial evaluation. To achieve high-performance, we employ staged compilation techniques and specialize the underlying relational data structures for a given Datalog specification. Experimentation on benchmarks for large-scale program analysis validates the superior performance of our approach over available Datalog tools and demonstrates our competitiveness with state-of-the-art handcrafted tools

How to Make a Soufflé; or, What Historians of the Book Need to Know about Bibliography

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Souffle/Spastizin regulates secretory granule maturation by sorting lysosomal cargo from immature secretory granule during zebrafish oogenesis

Successful reproduction of all sexually reproducing organisms mainly depends on the viability of the oocyte. The making of the oocyte is regulated at multiple level to ensure its quality where it carries the information from mother to the next generation. During oogenesis, apart from meiotic maturation cytoplasm also changes dynamically. The cellular transport pathways play an essential role in importing molecules from the mother and positioning them, which creates the polarity, axis and germplasm for future embryo. Vesicle trafficking is a vital transport process in all cells to import and deliver molecules to interact with the surrounding environment. This cellular mechanism is necessary for many biological processes like signal transduction, cytokinesis, polarity and lysosomal degradation. The discovery of many regulators (Rabs and SNAREs) in unicellular organisms showed the requirement of tight regulation in vesicle fission and fusion process. However, a forward genetic screen for yolk endocytosis in C.elegans discovered many novel regulators and a novel compartment, which are specific to multi-cellular organisms suggesting the presence of more complex regulation in vertebrates. Hence, finding new regulators are necessary to understand the process in vertebrates. We aimed at identifying novel, vertebrate regulators of oogenesis in zebrafish oocytes using a maternal-effect mutagenesis screen. We isolated a group of mutants, which lays opaque rather than transparent embryos. One of the mutants named soufflé (suf) has been mapped to a FYVE- Zinc finger protein by positional cloning. This FYVE domain binds to PI3P lipids, which are predominantly found on endosomal membranes. Biochemical analysis revealed that these mutants have a defect in yolk cleavage during oocyte maturation, which leads to the observed opaqueness (Dosch et al., 2004). Furthermore, electron microscopy analysis revealed that suf accumulates smaller endosomes, whereas in wild types they mature into functional yolk globules in the oocyte. These preliminary results raised the question that how does soufflé regulate trafficking during oogenesis and what is the molecular mechanism behind the defect in suf mutant. Endosomal analysis showed accumulation of Rab11 and fragmented lysosome. In-vivo trafficking assay showed no defect in endocytosis and endosomal recycling. Rab11 localizes to secretory granule and suf mutant accumulates immature secretory granule (ISG). In-vivo assay showed that suf fail to elevate the chorion after fertilization indicating a defect in exocytosis of dense core vesicle (DCV). Further analysis showed that suf mutant accumulate secretory granule without dense core resulted from defective sorting and vesicle fission from ISG. Surprisingly, we discovered the vesicle in cortical region with Abstract 13 many clathrin buds without fission accumulating in suf mutant using electron microscopy, consistent with accumulation of ISG marker VAMP4. Remarkably, chemical inhibition of dynamin function in the wild-type egg mimics suf mutant phenotype in cellular level and failed in chorion elevation. In addition, mis-organised F-actin showed the failure in exocytosis of vesicle. Rescue analysis with mutant construct showed that suf allele is a hypo morph. These results show that suf is necessary for sorting and fission during DCV formation. Sorting from ISG during DCV formation is also necessary for lysosomal biogenesis. We found that suf mutant lysosome did not receive cathepsin B, F and L, yolk-degrading proteases, explaining the opaque phenotype. Furthermore, vATPase subunit d1 is also missing in the vesicle of suf mutant oocytes. Analysis of lysosomal sorting receptors and adaptor revealed that suf mutant does not have a defect in M6PR and sortilin mediated pathway, but they show reduced LAMP carrier intermediate mediated by VPS41 and AP3. In addition, AP3 positive vesicles are reduced while AP3 accumulates more on secretory granule consistent with reduced VPS41 recruitment on secretory granule. VPS41-AP3 mediated lysosomal transport carries lysosomal enzymes, SNAREs and other membrane proteins. The VPS41 and AP3 mutant phenotype explains the reason for fragmented lysosome and failure in DCV formation phenotype in suf mutant. Bioinformatics prediction shows that suf has a clathrin heavy chain domain, which can form clathrin like coat like in VPS41. Suf interaction with AP5 further suggesting that suf may work as a coat protein like VPS41 for lysosomal transport. We discovered a novel function for suf in sorting of lysosomal cargo sorting from ISG results in successful DCV formation and lysosomal function, in the absence of suf both lysosome and DCV formation is affected. Interestingly, souffle mutation has been identified to cause progressive motor neuro-degeneration in human. This defect in DCV formation could be one reason for why the long motor neuron loses its connection and causes spasticity, since DCV is necessary for long-term potentiation. Hence, souffle mutant egg is an excellent model to study the molecular mechanism and disease pathology

Enhancing Weight Gain in Long-Term Care Residents at Risk for Weight Loss through Protein and Calorie Fortification.

Purpose of this study was to compare two methods of supplementing diets in order to provide additional protein and calories to increase body weight. The study consisted of two groups from the James H. Quillen Veterans Affair Medical Center Nursing Home Care Unit. Experimental group received foods fortified with increased calories and protein at mealtimes. Control group received nutrition supplements between meals. Fifteen subjects began the study. Analysis of weight change revealed that those in the experimental group had no weight change over the four months. Subjects in the control group gained an average of 4.8 lbs of body weight in the same period. The Mann-Whitney Test was used to determine if the weight changes were significantly different between groups. Analysis indicated that (p-value = 0.2550) there was no significant difference in body weight gain between the groups. A larger sample size would have improved the outcome of the study