An Implementation of the Language Lambda Prolog Organized around Higher-Order Pattern Unification

This thesis concerns the implementation of Lambda Prolog, a higher-order logic programming language that supports the lambda-tree syntax approach to representing and manipulating formal syntactic objects. Lambda Prolog achieves its functionality by extending a Prolog-like language by using typed lambda terms as data structures that it then manipulates via higher-order unification and some new program-level abstraction mechanisms. These additional features raise new implementation questions that must be adequately addressed for Lambda Prolog to be an effective programming tool. We consider these questions here, providing eventually a virtual machine and compilation based realization. A key idea is the orientation of the computation model of Lambda Prolog around a restricted version of higher-order unification with nice algorithmic properties and appearing to encompass most interesting applications. Our virtual machine embeds a treatment of this form of unification within the structure of the Warren Abstract Machine that is used in traditional Prolog implementations. Along the way, we treat various auxiliary issues such as the low-level representation of lambda terms, the implementation of reduction on such terms and the optimized processing of types in computation. We also develop an actual implementation of Lambda Prolog called Teyjus Version 2. A characteristic of this system is that it realizes an emulator for the virtual machine in the C language a compiler in the OCaml language. We present a treatment of the software issues that arise from this kind of mixing of languages within one system and we discuss issues relevant to the portability of our virtual machine emulator across arbitrary architectures. Finally, we assess the the efficacy of our various design ideas through experiments carried out using the system

Optimizing the runtime processing of types in a higher-order logic programming language

Abstract. The traditional purpose of types in programming languages of providing correctness assurances at compile time is increasingly being supplemented by a direct role for them in the computational process. In the specific context of typed logic programming, this is manifest in their effect on the unification operation. Their influence takes two different forms. First, in a situation where polymorphism is permitted, type information is needed to determine if different occurrences of the same name in fact denote an identical constant. Second, type information may determine the specific form of a binding for a variable. When types are needed for the second purpose as in the case of higher-order unification, these have to be available with every variable and constant. However, in many situations such as first-order and higher-order pattern unification it turns out that types have no impact on the variable binding process. As a consequence, type examination is needed in these situations only for the first of the two purposes described and even here a careful preprocessing can considerably reduce their runtime footprint. We develop a scheme for treating types in these contexts that exploits this observation. Under this scheme, type information is elided in most cases and is embedded into term structure when this is not entirely possible. Our approach obviates types when properties known as definitional genericity and type preservation are satisfied and has the advantage of working even when these conditions are violated.

Peptide-directed self-assembly of functionalized polymeric nanoparticles. Part II: Effects of nanoparticle composition on assembly behavior and multiple drug loading ability

Peptide-functionalized polymeric nanoparticles were designed and self-assembled into continuous nanoparticle fibers and three-dimensional scaffolds via ionic complementary peptide interaction. Different nanoparticle compositions can be designed to be appropriate for each desired drug, so that the release of each drug is individually controlled and the simultaneous sustainable release of multiple drugs is achieved in a single scaffold. A self-assembled scaffold membrane was incubated with NIH3T3 fibroblast cells in a culture dish that demonstrated non-toxicity and non-inhibition on cell proliferation. This type of nanoparticle scaffold combines the advantages of peptide self-assembly and the versatility of polymeric nanoparticle controlled release systems for tissue engineering. A novel nanoparticle scaffolding system is demonstrated using controlled-release, drug-loaded nanoparticles that yield ordered fibers and scaffolds using ionic complementary peptide-directed self-assembly. The scaffolding system possesses the advantages of individually controlling the release of each loaded drug and the ability to control their assembly sequence

The conserved misshapen-warts-Yorkie pathway acts in enteroblasts to regulate intestinal stem cells in Drosophila

Similar to the mammalian intestine, the Drosophila adult midgut has resident stem cells that support growth and regeneration. How the niche regulates intestinal stem cell activity in both mammals and flies is not well understood. Here, we show that the conserved germinal center protein kinase Misshapen restricts intestinal stem cell division by repressing the expression of the JAK-STAT pathway ligand Upd3 in differentiating enteroblasts. Misshapen, a distant relative to the prototypic Warts activating kinase Hippo, interacts with and activates Warts to negatively regulate the activity of Yorkie and the expression of Upd3. The mammalian Misshapen homolog MAP4K4 similarly interacts with LATS (Warts homolog) and promotes inhibition of YAP (Yorkie homolog). Together, this work reveals that the Misshapen-Warts-Yorkie pathway acts in enteroblasts to control niche signaling to intestinal stem cells. These findings also provide a model in which to study requirements for MAP4K4-related kinases in MST1/2-independent regulation of LATS and YAP

Alpha oscillatory activity is causally linked to working memory retention.

Although previous studies have reported correlations between alpha oscillations and the "retention" subprocess of working memory (WM), causal evidence has been limited in human neuroscience due to the lack of delicate modulation of human brain oscillations. Conventional transcranial alternating current stimulation (tACS) is not suitable for demonstrating the causal evidence for parietal alpha oscillations in WM retention because of its inability to modulate brain oscillations within a short period (i.e., the retention subprocess). Here, we developed an online phase-corrected tACS system capable of precisely correcting for the phase differences between tACS and concurrent endogenous oscillations. This system permits the modulation of brain oscillations at the target stimulation frequency within a short stimulation period and is here applied to empirically demonstrate that parietal alpha oscillations causally relate to WM retention. Our experimental design included both in-phase and anti-phase alpha-tACS applied to participants during the retention subprocess of a modified Sternberg paradigm. Compared to in-phase alpha-tACS, anti-phase alpha-tACS decreased both WM performance and alpha activity. These findings strongly support a causal link between alpha oscillations and WM retention and illustrate the broad application prospects of phase-corrected tACS