Type-Inference Based Short Cut Deforestation (nearly) without Inlining

Deforestation optimises a functional program by transforming it into another one that does not create certain intermediate data structures. In [ICFP'99] we presented a type-inference based deforestation algorithm which performs extensive inlining. However, across module boundaries only limited inlining is practically feasible. Furthermore, inlining is a non-trivial transformation which is therefore best implemented as a separate optimisation pass. To perform short cut deforestation (nearly) without inlining, Gill suggested to split definitions into workers and wrappers and inline only the small wrappers, which transfer the information needed for deforestation. We show that Gill's use of a function build limits deforestation and note that his reasons for using build do not apply to our approach. Hence we develop a more general worker/wrapper scheme without build. We give a type-inference based algorithm which splits definitions into workers and wrappers. Finally, we show that we can deforest more expressions with the worker/wrapper scheme than the algorithm with inlining

A Direct Algorithm for the Type Interference in the Rank 2 Fragment of the Second--Order λ-Calculus

We study the problem of type inference for a family of polymorphic type disciplines containing the power of Core-ML. This family comprises all levels of the stratification of the second-order lambda-calculus by "rank" of types. We show that typability is an undecidable problem at every rank k ≥ 3 of this stratification. While it was already known that typability is decidable at rank ≤ 2, no direct and easy-to-implement algorithm was available. To design such an algorithm, we develop a new notion of reduction and show how to use it to reduce the problem of typability at rank 2 to the problem of acyclic semi-unification. A by-product of our analysis is the publication of a simple solution procedure for acyclic semi-unification

Adding polymorphic abstraction to ML (detailed abstract)

The ML programming language restricts type polymorphism to occur only in the "let-in" construct and requires every occurrence of a formal parameter of a function (a lambda abstraction) to have the same type. Milner in 1978 refers to this restriction (which was adopted to help ML achieve automatic type inference) as a serious limitation. We show that this restriction can be relaxed enough to allow universal polymorphic abstraction without losing automatic type inference. This extension is equivalent to the rank-2 fragment of system F. We precisely characterize the additional program phrases (lambda terms) that can be typed with this extension and we describe typing anomalies both before and after the extension. We discuss how macros may be used to gain some of the power of rank-3 types without losing automatic type inference. We also discuss user-interface problems in how to inform the programmer of the possible types a program phrase may have.National Science Foundation (CCR-9113196

Principality and decidable type inference for finite-rank intersection types

Principality of typings is the property that for each typable term, there is a typing from which all other typings are obtained via some set of operations. Type inference is the problem of finding a typing for a given term, if possible. We define an intersection type system which has principal typings and types exactly the strongly normalizable λ-terms. More interestingly, every finite-rank restriction of this system (using Leivant's first notion of rank) has principal typings and also has decidable type inference. This is in contrast to System F where the finite rank restriction for every finite rank at 3 and above has neither principal typings nor decidable type inference. This is also in contrast to earlier presentations of intersection types where the status of these properties is not known for the finite-rank restrictions at 3 and above.Furthermore, the notion of principal typings for our system involves only one operation, substitution, rather than several operations (not all substitution-based) as in earlier presentations of principality for intersection types (of unrestricted rank). A unification-based type inference algorithm is presented using a new form of unification, β-unification.NATO (CRG 97107); National Science Foundation (CCR-9417382); Engineering and Physical Sciences Research Council (GR/L 36963

Gene expression profiling to study racial differences after heart transplantation.

BackgroundThe basis for increased mortality after heart transplantation in African Americans and other non-Caucasian racial groups is poorly defined. We hypothesized that increased risk of adverse events is driven by biologic factors. To test this hypothesis in the Invasive Monitoring Attenuation through Gene Expression (IMAGE) study, we determined whether the event rate of the primary outcome of acute rejection, graft dysfunction, death, or retransplantation varied by race as a function of calcineurin inhibitor (CNI) levels and gene expression profile (GEP) scores.MethodsWe determined the event rate of the primary outcome, comparing racial groups, stratified by time after transplant. Logistic regression was used to compute the relative risk across racial groups, and linear modeling was used to measure the dependence of CNI levels and GEP score on race.ResultsIn 580 patients monitored for a median of 19 months, the incidence of the primary end point was 18.3% in African Americans, 22.2% in other non-Caucasians, and 8.5% in Caucasians (p < 0.001). There were small but significant correlations of race and tacrolimus trough levels to the GEP score. Tacrolimus levels were similar among the races. Of patients receiving tacrolimus, other non-Caucasians had higher GEP scores than the other racial groups. African American recipients demonstrated a unique decrease in expression of the FLT3 gene in response to higher tacrolimus levels.ConclusionsAfrican Americans and other non-Caucasian heart transplant recipients were 2.5-times to 3-times more likely than Caucasians to experience outcome events in the Invasive Monitoring Attenuation through Gene Expression study. The increased risk of adverse outcomes may be partly due to the biology of the alloimmune response, which is less effectively inhibited at similar tacrolimus levels in minority racial groups

Hall Effect of Spin Waves in Frustrated Magnets

We examine a possible spin Hall effect for localized spin systems with no charge degrees of freedom. In this scenario, a longitudinal magnetic field gradient induces a transverse spin current carried by spin wave excitations with an anomalous velocity which is associated with the Berry curvature raised by spin chirality, in analogy with anomalous Hall effects in itinerant electron systems. Our argument is based on a semiclassical equations of motion applicable to general spin systems. Also, a microscopic model of frustrated magnets which exhibits the anamalous spin Hall effect is presented.Comment: 5 pages, title and presentation style are changed, accepted for publication in Phys. Rev. Let

The H3K27M mutation alters stem cell growth, epigenetic regulation, and differentiation potential

BACKGROUND: Neurodevelopmental disorders increase brain tumor risk, suggesting that normal brain development may have protective properties. Mutations in epigenetic regulators are common in pediatric brain tumors, highlighting a potentially central role for disrupted epigenetic regulation of normal brain development in tumorigenesis. For example, lysine 27 to methionine mutation (H3K27M) in the H3F3A gene occurs frequently in Diffuse Intrinsic Pontine Gliomas (DIPGs), the most aggressive pediatric glioma. As H3K27M mutation is necessary but insufficient to cause DIPGs, it is accompanied by additional mutations in tumors. However, how H3K27M alone increases vulnerability to DIPG tumorigenesis remains unclear. RESULTS: Here, we used human embryonic stem cell models with this mutation, in the absence of other DIPG contributory mutations, to investigate how H3K27M alters cellular proliferation and differentiation. We found that H3K27M increased stem cell proliferation and stem cell properties. It interfered with differentiation, promoting anomalous mesodermal and ectodermal gene expression during both multi-lineage and germ layer-specific cell specification, and blocking normal differentiation into neuroectoderm. H3K27M mutant clones exhibited transcriptomic diversity relative to the more homogeneous wildtype population, suggesting reduced fidelity of gene regulation, with aberrant expression of genes involved in stem cell regulation, differentiation, and tumorigenesis. These phenomena were associated with global loss of H3K27me3 and concordant loss of DNA methylation at specific genes in H3K27M-expressing cells. CONCLUSIONS: Together, these data suggest that H3K27M mutation disrupts normal differentiation, maintaining a partially differentiated state with elevated clonogenicity during early development. This disrupted response to early developmental cues could promote tissue properties that enable acquisition of additional mutations that cooperate with H3K27M mutation in genesis of DMG/DIPG. Therefore, this work demonstrates for the first time that H3K27M mutation confers vulnerability to gliomagenesis through persistent clonogenicity and aberrant differentiation and defines associated alterations of histone and DNA methylation

A Domain-Specific Language for Incremental and Modular Design of Large-Scale Verifiably-Safe Flow Networks (Preliminary Report)

We define a domain-specific language (DSL) to inductively assemble flow networks from small networks or modules to produce arbitrarily large ones, with interchangeable functionally-equivalent parts. Our small networks or modules are "small" only as the building blocks in this inductive definition (there is no limit on their size). Associated with our DSL is a type theory, a system of formal annotations to express desirable properties of flow networks together with rules that enforce them as invariants across their interfaces, i.e, the rules guarantee the properties are preserved as we build larger networks from smaller ones. A prerequisite for a type theory is a formal semantics, i.e, a rigorous definition of the entities that qualify as feasible flows through the networks, possibly restricted to satisfy additional efficiency or safety requirements. This can be carried out in one of two ways, as a denotational semantics or as an operational (or reduction) semantics; we choose the first in preference to the second, partly to avoid exponential-growth rewriting in the operational approach. We set up a typing system and prove its soundness for our DSL.Comment: In Proceedings DSL 2011, arXiv:1109.032

Mapping interactions with the chaperone network reveals factors that protect against tau aggregation.

A network of molecular chaperones is known to bind proteins ('clients') and balance their folding, function and turnover. However, it is often unclear which chaperones are critical for selective recognition of individual clients. It is also not clear why these key chaperones might fail in protein-aggregation diseases. Here, we utilized human microtubule-associated protein tau (MAPT or tau) as a model client to survey interactions between ~30 purified chaperones and ~20 disease-associated tau variants (~600 combinations). From this large-scale analysis, we identified human DnaJA2 as an unexpected, but potent, inhibitor of tau aggregation. DnaJA2 levels were correlated with tau pathology in human brains, supporting the idea that it is an important regulator of tau homeostasis. Of note, we found that some disease-associated tau variants were relatively immune to interactions with chaperones, suggesting a model in which avoiding physical recognition by chaperone networks may contribute to disease