260 research outputs found

    Relational Programming in miniKanren: Techniques, Applications, and Implementations

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    Thesis (Ph.D.) - Indiana University, Computer Sciences, 2009The promise of logic programming is that programs can be written relationally, without distinguishing between input and output arguments. Relational programs are remarkably flexible—for example, a relational type-inferencer also performs type checking and type inhabitation, while a relational theorem prover generates theorems as well as proofs and can even be used as a simple proof assistant. Unfortunately, writing relational programs is difficult, and requires many interesting and unusual tools and techniques. For example, a relational interpreter for a subset of Scheme might use nominal unification to support variable binding and scope, Constraint Logic Programming over Finite Domains (CLP(FD)) to implement relational arithmetic, and tabling to improve termination behavior. In this dissertation I present miniKanren, a family of languages specifically designed for relational programming, and which supports a variety of relational idioms and techniques. I show how miniKanren can be used to write interesting relational programs, including an extremely flexible lean tableau theorem prover and a novel constraint-free binary arithmetic system with strong termination guarantees. I also present interesting and practical techniques used to implement miniKanren, including a nominal unifier that uses triangular rather than idempotent substitutions and a novel “walk”-based algorithm for variable lookup in triangular substitutions. The result of this research is a family of languages that supports a variety of relational idioms and techniques, making it feasible and useful to write interesting programs as relations

    Lytic switch protein (ORF50) response element in the Kaposi’s sarcoma-associated herpesvirus K8 promoter is located within but does not require a palindromic structure

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    Kaposi's sarcoma-associated virus (KSHV) ORF50 protein induces lytic replication and activates the K8 promoter. We show that ORF50-induced and tetradecanoyl phorbol acetate (TPA) induced K8 transcripts initiated from the same start site. A newly identified palindrome (PAL2), containing a 12-bp response region required for ORF50-induced activation in lymphoid cells, was identified in the K8 promoter. Specific DNA binding of bacterially expressed ORF50 was not seen with the K8 promoter despite specific binding to the PAN promoter. The new palindrome shared homology with a previously described ORF50 response element (50RE(K8) and 50RE(57)). We demonstrate that the new 50RE(K8) (50RE(K8-PAL2)) is not the palindrome per se. Instead, the response element is buried within the right arm of the palindrome. We propose that the complexity of the K8 response elements reflects the complexity of mechanisms used by ORF50 during viral reactivation

    A Simple Complete Search for Logic Programming

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    Here, we present a family of complete interleaving depth-first search strategies for embedded, domain-specific logic languages. We derive our search family from a stream-based implementation of incomplete depth-first search. The DSL\u27s programs\u27 texts induce particular strategies guaranteed to be complete

    Cytoplasmic Dynein Heavy Chain 1b Is Required for Flagellar Assembly in Chlamydomonas

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    A second cytoplasmic dynein heavy chain (cDhc) has recently been identified in several organisms, and its expression pattern is consistent with a possible role in axoneme assembly. We have used a genetic approach to ask whether cDhc1b is involved in flagellar assembly in Chlamydomonas. Using a modified PCR protocol, we recovered two cDhc sequences distinct from the axonemal Dhc sequences identified previously. cDhc1a is closely related to the major cytoplasmic Dhc, whereas cDhc1b is closely related to the minor cDhc isoform identified in sea urchins, Caenorhabditis elegans, and Tetrahymena. TheChlamydomonas cDhc1b transcript is a low-abundance mRNA whose expression is enhanced by deflagellation. To determine its role in flagellar assembly, we screened a collection of stumpy flagellar (stf) mutants generated by insertional mutagenesis and identified two strains in which portions of the cDhc1bgene have been deleted. The two mutants assemble short flagellar stumps (<1–2 μm) filled with aberrant microtubules, raft-like particles, and other amorphous material. The results indicate that cDhc1b is involved in the transport of components required for flagellar assembly in Chlamydomonas

    Gene Expression from the ORF50/K8 Region of Kaposi's Sarcoma-Associated Herpesvirus

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    The ORF50 gene of Kaposi's sarcoma (KS)-associated herpesvirus, or human herpesvirus 8 (KSHV), activates viral replication and is weakly homologous to the herpesvirus family of R transactivators; therefore, the transcription and translation events from this region of KSHV are key events in viral reactivation. We demonstrate that ORF50 is expressed in a bicistronic message after induction of the viral lytic cycle. ORF50 migrated as a series of polypeptides: the major ones as 119 and 101 kDa, respectively. Using 3' rapid amplification of cDNA ends, RT-PCR, and cDNA library screening, we demonstrate that the major ORF50 transcript also encodes K8. The ORF50/K8 transcript was resistant to cyclohexamide, whereas the K8 transcript was only partially resistant to cyclohexamide at early timepoints. Both transcripts showed partial resistance after 12 h of phorbol ester induction. Using a GAL4-ORF50 fusion protein expression vector, we demonstrate that the transactivation domain of ORF50 resides within a 160-amino-acid region of the carboxyl portion of the ORF. Upstream regions of both ORF50 and K8 have basal promoter activity in KSHV-infected cells. K8, which had sequence homology to Bzip proteins, did not activate either promoter. However, both promoters were activated after cotransfection of ORF50 in BCBL-1 cells

    Phase II prospective randomized trial of weight loss prior to radical prostatectomy.

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    BACKGROUND:Obesity is associated with poorly differentiated and advanced prostate cancer and increased mortality. In preclinical models, caloric restriction delays prostate cancer progression and prolongs survival. We sought to determine if weight loss (WL) in men with prostate cancer prior to radical prostatectomy affects tumor apoptosis and proliferation, and if WL effects other metabolic biomarkers. METHODS:In this Phase II prospective trial, overweight and obese men scheduled for radical prostatectomy were randomized to a 5-8 week WL program consisting of standard structured energy-restricted meal plans (1200-1500 Kcal/day) and physical activity or to a control group. The primary endpoint was apoptotic index in the radical prostatectomy malignant epithelium. Secondary endpoints were proliferation (Ki67) in the radical prostatectomy tissue, body weight, body mass index (BMI), waist to hip ratio, body composition, and serum PSA, insulin, triglyceride, cholesterol, testosterone, estradiol, leptin, adiponectin, interleukin 6, interleukin 8, insulin-like growth factor 1, and IGF binding protein 1. RESULTS:In total 23 patients were randomized to the WL intervention and 21 patients to the control group. Subjects in the intervention group had significantly more weight loss (WL:-3.7 ± 0.5 kg; Control:-1.6 ± 0.5 kg; p = 0.007) than the control group and total fat mass was significantly reduced (WL:-2.1 ± 0.4; Control: 0.1 ± 0.3; p = 0.015). There was no significant difference in apoptotic or proliferation index between the groups. Among the other biomarkers, triglyceride, and insulin levels were significantly decreased in the WL compared with the control group. CONCLUSIONS:In summary, this short-term WL program prior to radical prostatectomy resulted in significantly more WL in the intervention vs. the control group and was accompanied by significant reductions in body fat mass, circulating triglycerides, and insulin. However, no significant changes were observed in malignant epithelium apoptosis or proliferation. Future studies should consider a longer term or more intensive weight loss intervention

    Discordance between imaging and immunohistochemistry in unilateral primary aldosteronism

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    Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139975/1/cen13442.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139975/2/cen13442_am.pd
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