1,193 research outputs found

    Functional Big-step Semantics

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    When doing an interactive proof about a piece of software, it is important that the underlying programming language’s semantics does not make the proof unnecessarily difficult or unwieldy. Both smallstep and big-step semantics are commonly used, and the latter is typically given by an inductively defined relation. In this paper, we consider an alternative: using a recursive function akin to an interpreter for the language. The advantages include a better induction theorem, less duplication, accessibility to ordinary functional programmers, and the ease of doing symbolic simulation in proofs via rewriting. We believe that this style of semantics is well suited for compiler verification, including proofs of divergence preservation. We do not claim the invention of this style of semantics: our contribution here is to clarify its value, and to explain how it supports several language features that might appear to require a relational or small-step approach. We illustrate the technique on a simple imperative language with C-like for-loops and a break statement, and compare it to a variety of other approaches. We also provide ML and lambda-calculus based examples to illustrate its generality

    Cisplatin-induced emesis: systematic review and meta-analysis of the ferret model and the effects of 5-HT3 receptor antagonists

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    PURPOSE: The ferret cisplatin emesis model has been used for ~30 years and enabled identification of clinically used anti-emetics. We provide an objective assessment of this model including efficacy of 5-HT(3) receptor antagonists to assess its translational validity. METHODS: A systematic review identified available evidence and was used to perform meta-analyses. RESULTS: Of 182 potentially relevant publications, 115 reported cisplatin-induced emesis in ferrets and 68 were included in the analysis. The majority (n = 53) used a 10 mg kg(−1) dose to induce acute emesis, which peaked after 2 h. More recent studies (n = 11) also used 5 mg kg(−1), which induced a biphasic response peaking at 12 h and 48 h. Overall, 5-HT(3) receptor antagonists reduced cisplatin (5 mg kg(−1)) emesis by 68% (45–91%) during the acute phase (day 1) and by 67% (48–86%) and 53% (38–68%, all P < 0.001), during the delayed phase (days 2, 3). In an analysis focused on the acute phase, the efficacy of ondansetron was dependent on the dosage and observation period but not on the dose of cisplatin. CONCLUSION: Our analysis enabled novel findings to be extracted from the literature including factors which may impact on the applicability of preclinical results to humans. It reveals that the efficacy of ondansetron is similar against low and high doses of cisplatin. Additionally, we showed that 5-HT(3) receptor antagonists have a similar efficacy during acute and delayed emesis, which provides a novel insight into the pharmacology of delayed emesis in the ferret

    Massive stars as thermonuclear reactors and their explosions following core collapse

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    Nuclear reactions transform atomic nuclei inside stars. This is the process of stellar nucleosynthesis. The basic concepts of determining nuclear reaction rates inside stars are reviewed. How stars manage to burn their fuel so slowly most of the time are also considered. Stellar thermonuclear reactions involving protons in hydrostatic burning are discussed first. Then I discuss triple alpha reactions in the helium burning stage. Carbon and oxygen survive in red giant stars because of the nuclear structure of oxygen and neon. Further nuclear burning of carbon, neon, oxygen and silicon in quiescent conditions are discussed next. In the subsequent core-collapse phase, neutronization due to electron capture from the top of the Fermi sea in a degenerate core takes place. The expected signal of neutrinos from a nearby supernova is calculated. The supernova often explodes inside a dense circumstellar medium, which is established due to the progenitor star losing its outermost envelope in a stellar wind or mass transfer in a binary system. The nature of the circumstellar medium and the ejecta of the supernova and their dynamics are revealed by observations in the optical, IR, radio, and X-ray bands, and I discuss some of these observations and their interpretations.Comment: To be published in " Principles and Perspectives in Cosmochemistry" Lecture Notes on Kodai School on Synthesis of Elements in Stars; ed. by Aruna Goswami & Eswar Reddy, Springer Verlag, 2009. Contains 21 figure

    Left Hemisphere Specialization for Oro-Facial Movements of Learned Vocal Signals by Captive Chimpanzees

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    The left hemisphere of the human brain is dominant in the production of speech and signed language. Whether similar lateralization of function for communicative signal production is present in other primates remains a topic of considerable debate. In the current study, we examined whether oro-facial movements associated with the production of learned attention-getting sounds are differentially lateralized compared to facial expressions associated with the production of species-typical emotional vocalizations in chimpanzees.Still images captured from digital video were used to quantify oro-facial asymmetries in the production of two attention-getting sounds and two species-typical vocalizations in a sample of captive chimpanzees. Comparisons of mouth asymmetries during production of these sounds revealed significant rightward biased asymmetries for the attention-getting sounds and significant leftward biased asymmetries for the species-typical sounds.These results suggest that the motor control of oro-facial movements associated with the production of learned sounds is lateralized to the left hemisphere in chimpanzees. Furthermore, the findings suggest that the antecedents for lateralization of human speech may have been present in the common ancestor of chimpanzees and humans approximately 5 mya and are not unique to the human lineage

    Identification of Continuous Human B-Cell Epitopes in the Envelope Glycoprotein of Dengue Virus Type 3 (DENV-3)

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    BACKGROUND:Dengue virus infection is a growing global public health concern in tropical and subtropical regions of the world. Dengue vaccine development has been hampered by concerns that cross-reactive immunological memory elicited by a candidate vaccine could increase the risk of development of more severe clinical forms. One possible strategy to reduce risks associated with a dengue vaccine is the development of a vaccine composed of selected critical epitopes of each of the serotypes. METHODOLOGY/PRINCIPAL FINDINGS:Synthetic peptides were used to identify B-cell epitopes in the envelope (E) glycoprotein of dengue virus type 3 (DENV-3). Eleven linear, immunodominant epitopes distributed in five regions at amino acid (aa) positions: 51-65, 71-90, 131-170, 196-210 and 246-260 were identified by employing an enzyme- linked immunosorbent assay (ELISA), using a pool of human sera from dengue type 3 infected individuals. Peptides 11 (aa51-65), 27 and 28 (aa131-150) also reacted with dengue 1 (DENV-1) and dengue 2 (DENV-2) patient sera as analyzed through the ROC curves generated for each peptide by ELISA and might have serotype specific diagnostic potential. Mice immunized against each one of the five immunogenic regions showed epitopes 51-65, 131-170, 196-210 and 246-260 elicited the highest antibody response and epitopes131-170, 196-210 and 246-260, elicited IFN-gamma production and T CD4+ cell response, as evaluated by ELISA and ELISPOT assays respectively. CONCLUSIONS/SIGNIFICANCE:Our study identified several useful immunodominant IgG-specific epitopes on the envelope of DENV-3. They are important tools for understanding the mechanisms involved in antibody dependent enhancement and immunity. If proven protective and safe, in conjunction with others well-documented epitopes, they might be included into a candidate epitope-based vaccine
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