The Essence of Nested Composition

Calculi with disjoint intersection types support an introduction form for intersections called the merge operator, while retaining a coherent semantics. Disjoint intersections types have great potential to serve as a foundation for powerful, flexible and yet type-safe and easy to reason OO languages. This paper shows how to significantly increase the expressive power of disjoint intersection types by adding support for nested subtyping and composition, which enables simple forms of family polymorphism to be expressed in the calculus. The extension with nested subtyping and composition is challenging, for two different reasons. Firstly, the subtyping relation that supports these features is non-trivial, especially when it comes to obtaining an algorithmic version. Secondly, the syntactic method used to prove coherence for previous calculi with disjoint intersection types is too inflexible, making it hard to extend those calculi with new features (such as nested subtyping). We show how to address the first problem by adapting and extending the Barendregt, Coppo and Dezani (BCD) subtyping rules for intersections with records and coercions. A sound and complete algorithmic system is obtained by using an approach inspired by Pierce\u27s work. To address the second problem we replace the syntactic method to prove coherence, by a semantic proof method based on logical relations. Our work has been fully formalized in Coq, and we have an implementation of our calculus

Row and Bounded Polymorphism via Disjoint Polymorphism

Polymorphism and subtyping are important features in mainstream OO languages. The most common way to integrate the two is via ?_{< :} style bounded quantification. A closely related mechanism is row polymorphism, which provides an alternative to subtyping, while still enabling many of the same applications. Yet another approach is to have type systems with intersection types and polymorphism. A recent addition to this design space are calculi with disjoint intersection types and disjoint polymorphism. With all these alternatives it is natural to wonder how they are related. This paper provides an answer to this question. We show that disjoint polymorphism can recover forms of both row polymorphism and bounded polymorphism, while retaining key desirable properties, such as type-safety and decidability. Furthermore, we identify the extra power of disjoint polymorphism which enables additional features that cannot be easily encoded in calculi with row polymorphism or bounded quantification alone. Ultimately we expect that our work is useful to inform language designers about the expressive power of those common features, and to simplify implementations and metatheory of feature-rich languages with polymorphism and subtyping

Reduced anthropogenic aerosol radiative forcing caused by biogenic new particle formation

The magnitude of aerosol radiative forcing caused by anthropogenic emissions depends on the baseline state of the atmosphere under pristine preindustrial conditions. Measurements show that particle formation in atmospheric conditions can occur solely from biogenic vapors. Here, we evaluate the potential effect of this source of particles on preindustrial cloud condensation nuclei (CCN) concentrations and aerosol–cloud radiative forcing over the industrial period. Model simulations show that the pure biogenic particle formation mechanism has a much larger relative effect on CCN concentrations in the preindustrial atmosphere than in the present atmosphere because of the lower aerosol concentrations. Consequently, preindustrial cloud albedo is increased more than under present day conditions, and therefore the cooling forcing of anthropogenic aerosols is reduced. The mechanism increases CCN concentrations by 20–100% over a large fraction of the preindustrial lower atmosphere, and the magnitude of annual global mean radiative forcing caused by changes of cloud albedo since 1750 is reduced by 0.22 W m^(−2) (27%) to −0.60 W m^(−2). Model uncertainties, relatively slow formation rates, and limited available ambient measurements make it difficult to establish the significance of a mechanism that has its dominant effect under preindustrial conditions. Our simulations predict more particle formation in the Amazon than is observed. However, the first observation of pure organic nucleation has now been reported for the free troposphere. Given the potentially significant effect on anthropogenic forcing, effort should be made to better understand such naturally driven aerosol processes

A novel C-terminal HSP90 inhibitor KU135 induces apoptosis and cell cycle arrest in melanoma cells

Heat shock protein 90 (Hsp90) is differentially expressed in tumor cells including melanoma and involved in proper folding, stabilization and regulation of cellular proteins. We investigated a novobiocin-derived Hsp90 C-terminal inhibitor, KU135, for anti-proliferative effects in melanoma cells. The results indicate that KU135 reduced cell viability and cell proliferation in melanoma cells and IC50 values for A735(DRO), M14(NPA), B16F10 and SKMEL28 cells were 0.82, 0.92, 1.33 and 1.30 M respectively. KU135 induced a more potent anti-proliferative effect in most melanoma cells versus N-terminal Hsp90 inhibitor 17AAG. KU135 induced apoptosis in melanoma cells, as indicated by annexin V/PI staining, reduction in the mitochondrial membrane potential, mitochondrial cytochrome C release and caspase 3 activation. KU135 reduced levels of Hsp90 client proteins Akt, BRAF, RAF-1, cyclin B and cdc25 proteins. Additionally, it reduced Hsp70, Hsp90 paralog, GRP94 and HSF1 levels. KU135 induced strong G2/M cell cycle arrest, associated with decreased expression of cdc25c, cyclin B and increased phosphorylation of cdc25c. These finding show that KU135 reduced cell survival, proliferation, and induces apoptosis in melanoma cells. We suggest that KU135 may be a potential candidate for cancer therapy against melanoma

Color Capable Sub-Pixel Resolving Optofluidic Microscope and Its Application to Blood Cell Imaging for Malaria Diagnosis

Miniaturization of imaging systems can significantly benefit clinical diagnosis in challenging environments, where access to physicians and good equipment can be limited. Sub-pixel resolving optofluidic microscope (SROFM) offers high-resolution imaging in the form of an on-chip device, with the combination of microfluidics and inexpensive CMOS image sensors. In this work, we report on the implementation of color SROFM prototypes with a demonstrated optical resolution of 0.66 µm at their highest acuity. We applied the prototypes to perform color imaging of red blood cells (RBCs) infected with Plasmodium falciparum, a particularly harmful type of malaria parasites and one of the major causes of death in the developing world

Exploiting Dual-Gate Ambipolar CNFETs for Scalable Machine Learning Classification

Ambipolar carbon nanotube based field-effect transistors (AP-CNFETs) exhibit unique electrical characteristics, such as tri-state operation and bi-directionality, enabling systems with complex and reconfigurable computing. In this paper, AP-CNFETs are used to design a mixed-signal machine learning (ML) classifier. The classifier is designed in SPICE with feature size of 15 nm and operates at 250 MHz. The system is demonstrated based on MNIST digit dataset, yielding 90% accuracy and no accuracy degradation as compared with the classification of this dataset in Python. The system also exhibits lower power consumption and smaller physical size as compared with the state-of-the-art CMOS and memristor based mixed-signal classifiers

Scanning the human genome at kilobase resolution

Normal genome variation and pathogenic genome alteration frequently affect small regions in the genome. Identifying those genomic changes remains a technical challenge. We report here the development of the DGS (Ditag Genome Scanning) technique for high-resolution analysis of genome structure. The basic features of DGS include (1) use of high-frequent restriction enzymes to fractionate the genome into small fragments; (2) collection of two tags from two ends of a given DNA fragment to form a ditag to represent the fragment; (3) application of the 454 sequencing system to reach a comprehensive ditag sequence collection; (4) determination of the genome origin of ditags by mapping to reference ditags from known genome sequences; (5) use of ditag sequences directly as the sense and antisense PCR primers to amplify the original DNA fragment. To study the relationship between ditags and genome structure, we performed a computational study by using the human genome reference sequences as a model, and analyzed the ditags experimentally collected from the well-characterized normal human DNA GM15510 and the leukemic human DNA of Kasumi-1 cells. Our studies show that DGS provides a kilobase resolution for studying genome structure with high specificity and high genome coverage. DGS can be applied to validate genome assembly, to compare genome similarity and variation in normal populations, and to identify genomic abnormality including insertion, inversion, deletion, translocation, and amplification in pathological genomes such as cancer genomes