Global profiling of stimulus-induced polyadenylation in cells using a poly(A) trap

Polyadenylation of mRNA leads to increased protein expression in response to diverse stimuli, but it is difficult to identify mRNAs that become polyadenylated in living cells. Here we describe a click chemistry-compatible nucleoside analog that is selectively incorporated into poly(A) tails of transcripts in cells. Next-generation sequencing of labeled mRNAs enables a transcriptome-wide profile of polyadenylation and provides insights into the mRNA sequence elements that are correlated with polyadenylation

A Finite Representation of the Narrowing Space

The final publication is available at Springer via http://dx.doi.org/10.1007/978-3-319-14125-1_4Narrowing basically extends rewriting by allowing free variables in terms and by replacing matching with unification. As a consequence, the search space of narrowing becomes usually infinite, as in logic programming. In this paper, we introduce the use of some operators that allow one to always produce a finite data structure that still represents all the narrowing derivations. Furthermore, we extract from this data structure a novel, compact equational representation of the (possibly infinite) answers computed by narrowing for a given initial term. Both the finite data structure and the equational representation of the computed answers might be useful in a number of areas, like program comprehension, static analysis, program transformation, etc.Nishida, N.; Vidal, G. (2013). A Finite Representation of the Narrowing Space. En Logic-Based Program Synthesis and Transformation. Springer. 54-71. doi:10.1007/978-3-319-14125-1_4S5471Albert, E., Vidal, G.: The Narrowing-Driven Approach to Functional Logic Program Specialization. New Generation Computing 20(1), 3–26 (2002)Alpuente, M., Falaschi, M., Vidal, G.: Partial Evaluation of Functional Logic Programs. ACM Transactions on Programming Languages and Systems 20(4), 768–844 (1998)Alpuente, M., Falaschi, M., Vidal, G.: Compositional Analysis for Equational Horn Programs. In: Rodríguez-Artalejo, M., Levi, G. (eds.) ALP 1994. LNCS, vol. 850, pp. 77–94. Springer, Heidelberg (1994)Antoy, S., Ariola, Z.: Narrowing the Narrowing Space. In: Hartel, P.H., Kuchen, H. (eds.) PLILP 1997. LNCS, vol. 1292, pp. 1–15. Springer, Heidelberg (1997)Arts, T., Giesl, J.: Termination of term rewriting using dependency pairs. Theoretical Computer Science 236(1–2), 133–178 (2000)Arts, T., Zantema, H.: Termination of Logic Programs Using Semantic Unification. In: Proietti, M. (ed.) LOPSTR 1995. LNCS, vol. 1048, pp. 219–233. Springer, Heidelberg (1996)Baader, F., Nipkow, T.: Term Rewriting and All That. Cambridge University Press (1998)Bae, K., Escobar, S., Meseguer, J.: Abstract Logical Model Checking of Infinite-State Systems Using Narrowing. In: Proceedings of the 24th International Conference on Rewriting Techniques and Applications. LIPIcs, vol. 21, pp. 81–96. Schloss Dagstuhl - Leibniz-Zentrum für Informatik (2013)De Schreye, D., Glück, R., Jørgensen, J., Leuschel, M., Martens, B., Sørensen, M.: Conjunctive partial deduction: foundations, control, algorihtms, and experiments. Journal of Logic Programming 41(2&3), 231–277 (1999)Escobar, S., Meadows, C., Meseguer, J.: A rewriting-based inference system for the NRL Protocol Analyzer and its meta-logical properties. Theoretical Computer Science 367(1–2), 162–202 (2006)Escobar, S., Meseguer, J.: Symbolic Model Checking of Infinite-State Systems Using Narrowing. In: Baader, F. (ed.) RTA 2007. LNCS, vol. 4533, pp. 153–168. Springer, Heidelberg (2007)Fribourg, L.: SLOG: A Logic Programming Language Interpreter Based on Clausal Superposition and Rewriting. In: Proceedings of the Symposium on Logic Programming, pp. 172–185. IEEE Press (1985)Gnaedig, I., Kirchner, H.: Proving weak properties of rewriting. Theoretical Computer Science 412(34), 4405–4438 (2011)Hanus, M.: The integration of functions into logic programming: From theory to practice. Journal of Logic Programming 19&20, 583–628 (1994)Hanus, M. (ed.): Curry: An integrated functional logic language (vers. 0.8.3) (2012). http://www.curry-language.orgHermenegildo, M., Rossi, F.: On the Correctness and Efficiency of Independent And-Parallelism in Logic Programs. In: Lusk, E., Overbeck, R. (eds.) Proceedings of the 1989 North American Conf. on Logic Programming, pp. 369–389. The MIT Press, Cambridge (1989)Hölldobler, S. (ed.): Foundations of Equational Logic Programming. LNCS, vol. 353. Springer, Heidelberg (1989)Meseguer, J., Thati, P.: Symbolic Reachability Analysis Using Narrowing and its Application to Verification of Cryptographic Protocols. Electronic Notes in Theoretical Computer Science 117, 153–182 (2005)Middeldorp, A., Okui, S.: A Deterministic Lazy Narrowing Calculus. Journal of Symbolic Computation 25(6), 733–757 (1998)Nishida, N., Sakai, M., Sakabe, T.: Generation of Inverse Computation Programs of Constructor Term Rewriting Systems. IEICE Transactions on Information and Systems J88–D–I(8), 1171–1183 (2005) (in Japanese)Nishida, N., Sakai, M., Sakabe, T.: Partial Inversion of Constructor Term Rewriting Systems. In: Giesl, J. (ed.) RTA 2005. LNCS, vol. 3467, pp. 264–278. Springer, Heidelberg (2005)Nishida, N., Vidal, G.: Program inversion for tail recursive functions. In: Schmidt-Schauß, M. (ed.) Proceedings of the 22nd International Conference on Rewriting Techniques and Applications. LIPIcs, vol. 10, pp. 283–298. Schloss Dagstuhl - Leibniz-Zentrum für Informatik (2011)Nishida, N., Vidal, G.: Computing More Specific Versions of Conditional Rewriting Systems. In: Albert, E. (ed.) LOPSTR 2012. LNCS, vol. 7844, pp. 137–154. Springer, Heidelberg (2013)Nutt, W., Réty, P., Smolka, G.: Basic Narrowing Revisited. Journal of Symbolic Computation 7(3/4), 295–317 (1989)Ohlebusch, E.: Advanced Topics in Term Rewriting. Springer, London, UK (2002)Palamidessi, C.: Algebraic Properties of Idempotent Substitutions. In: Paterson, M. (ed.) ICALP 1990. LNCS, vol. 443, pp. 386–399. Springer, Heidelberg (1990)Ramos, J.G., Silva, J., Vidal, G.: Fast Narrowing-Driven Partial Evaluation for Inductively Sequential Systems. In: Danvy, O., Pierce, B.C. (eds.) Proceedings of the 10th ACM SIGPLAN International Conference on Functional Programming, pp. 228–239. ACM Press (2005)Slagle, J.R.: Automated theorem-proving for theories with simplifiers, commutativity and associativity. Journal of the ACM 21(4), 622–642 (1974

From Boolean Equalities to Constraints

Although functional as well as logic languages use equality to discriminate between logically different cases, the operational meaning of equality is different in such languages. Functional languages reduce equational expressions to their Boolean values, True or False, logic languages use unification to check the validity only and fail otherwise. Consequently, the language Curry, which amalgamates functional and logic programming features, offers two kinds of equational expressions so that the programmer has to distinguish between these uses. We show that this distinction can be avoided by providing an analysis and transformation method that automatically selects the appropriate operation. Without this distinction in source programs, the language design can be simplified and the execution of programs can be optimized. As a consequence, we show that one kind of equational expressions is sufficient and unification is nothing else than an optimization of Boolean equality

White light thermoplasmonic activated gold nanorod arrays enable the photo-thermal disinfection of medical tools from bacterial contamination

The outspread of bacterial pathogens causing severe infections and spreading rapidly, especially among hospitalized patients, is worrying and represents a global public health issue. Current disinfection techniques are becoming insufficient to counteract the spread of these pathogens because they carry multiple antibiotic-resistance genes. For this reason, a constant need exists for new technological solutions that rely on physical methods rather than chemicals. Nanotechnology support provides novel and unexplored opportunities to boost groundbreaking, next-gen solutions. With the help of plasmonic-assisted nanomaterials, we present and discuss our findings in innovative bacterial disinfection techniques. Gold nanorods (AuNRs) immobilized on rigid substrates are utilized as efficient white light-to-heat transducers (thermoplasmonic effect) for photo-thermal (PT) disinfection. The resulting AuNRs array shows a high sensitivity change in refractive index and an extraordinary capability in converting white light to heat, producing a temperature change greater than 50 °C in a few minute interval illumination time. Results were validated using a theoretical approach based on a diffusive heat transfer model. Experiments performed with a strain of Escherichia coli as a model microorganism confirm the excellent capability of the AuNRs array to reduce the bacteria viability upon white light illumination. Conversely, the E. coli cells remain viable without white light illumination, which also confirms the lack of intrinsic toxicity of the AuNRs array. The PT transduction capability of the AuNRs array is utilized to produce white light heating of medical tools used during surgical treatments, generating a temperature increase that can be controlled and is suitable for disinfection. Our findings are pioneering a new opportunity for healthcare facilities since the reported methodology allows non-hazardous disinfection of medical devices by simply employing a conventional white light lamp

Analysis of anemia and iron supplementation among glioblastoma patients reveals sex-biased association between anemia and survival

The association between anemia and outcomes in glioblastoma patients is unclear. We analyzed data from 1346 histologically confirmed adult glioblastoma patients in the TriNetX Research Network. Median hemoglobin and hematocrit levels were quantified for 6 months following diagnosis and used to classify patients as anemic or non-anemic. Associations of anemia and iron supplementation of anemic patients with median overall survival (median-OS) were then studied. Among 1346 glioblastoma patients, 35.9% of male and 40.5% of female patients were classified as anemic using hemoglobin-based WHO guidelines. Among males, anemia was associated with reduced median-OS compared to matched non-anemic males using hemoglobin (HR 1.24; 95% CI 1.00-1.53) or hematocrit-based cutoffs (HR 1.28; 95% CI 1.03-1.59). Among females, anemia was not associated with median-OS using hemoglobin (HR 1.00; 95% CI 0.78-1.27) or hematocrit-based cutoffs (HR: 1.10; 95% CI 0.85-1.41). Iron supplementation of anemic females trended toward increased median-OS (HR 0.61; 95% CI 0.32-1.19) although failing to reach statistical significance whereas no significant association was found in anemic males (HR 0.85; 95% CI 0.41-1.75). Functional transferrin-binding assays confirmed sexually dimorphic binding in resected patient samples indicating underlying differences in iron biology. Anemia among glioblastoma patients exhibits a sex-specific association with survival

Artificial Intelligence

Contains research objectives and reports on five research projects.Computation Center, M.I.T

Toward Human-Carnivore Coexistence: Understanding Tolerance for Tigers in Bangladesh

Fostering local community tolerance for endangered carnivores, such as tigers (Panthera tigris), is a core component of many conservation strategies. Identification of antecedents of tolerance will facilitate the development of effective tolerance-building conservation action and secure local community support for, and involvement in, conservation initiatives. We use a stated preference approach for measuring tolerance, based on the ‘Wildlife Stakeholder Acceptance Capacity’ concept, to explore villagers’ tolerance levels for tigers in the Bangladesh Sundarbans, an area where, at the time of the research, human-tiger conflict was severe. We apply structural equation modeling to test an a priori defined theoretical model of tolerance and identify the experiential and psychological basis of tolerance in this community. Our results indicate that beliefs about tigers and about the perceived current tiger population trend are predictors of tolerance for tigers. Positive beliefs about tigers and a belief that the tiger population is not currently increasing are both associated with greater stated tolerance for the species. Contrary to commonly-held notions, negative experiences with tigers do not directly affect tolerance levels; instead, their effect is mediated by villagers’ beliefs about tigers and risk perceptions concerning human-tiger conflict incidents. These findings highlight a need to explore and understand the socio-psychological factors that encourage tolerance towards endangered species. Our research also demonstrates the applicability of this approach to tolerance research to a wide range of socio-economic and cultural contexts and reveals its capacity to enhance carnivore conservation efforts worldwide

Mechanisms for the formation of benzene in the atmosphere of Titan

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95336/1/jgre1586.pd

Mid-Pleistocene climate transition drives net mass loss from rapidly uplifting St. Elias Mountains, Alaska

Erosion, sediment production and routing on a tectonically active continental margin reflect both tectonic and climatic processes; partitioning the relative importance of these processes remains controversial. Gulf of Alaska contains a preserved sedimentary record of Yakutat Terrane collision with North America. Because tectonic convergence in the coastal St. Elias orogen has been roughly constant for 6 Myr, variations in its eroded sediments preserved in the offshore Surveyor Fan constrain a budget of tectonic material influx, erosion, and sediment output. Seismically imaged sediment volumes calibrated with chronologies derived from Integrated Ocean Drilling Program boreholes shows that erosion accelerated in response to Northern Hemisphere glacial intensification (~2.7 Ma) and that the 900-km long Surveyor Channel inception appears to correlate with this event. However, tectonic influx exceeded integrated sediment efflux over the interval 2.8-1.2 Ma. Volumetric erosion accelerated following the onset of quasi-periodic (~100-kyr) glacial cycles in the mid-Pleistocene climate transition (1.2-0.7 Ma). Since then erosion and transport of material out of the orogen has outpaced tectonic influx by 50-80%. Such a rapid net mass loss explains apparent increases in exhumation rates inferred onshore from exposure dates and mapped out-of-sequence fault patterns. The 1.2 Myr mass budget imbalance must relax back toward equilibrium in balance with tectonic influx over the time scale of orogenic wedge response (Myrs). The St. Elias Range provides a key example of how active orogenic systems respond to transient mass fluxes, and the possible influence of climate driven erosive processes that diverge from equilibrium on the million-year scale

Global and local controlson continental margin stratigraphy

Integrated Ocean Drilling Program (IODP) Expedition 317 was devoted to understanding the relative importance of global sea level (eustasy) versus local tectonic and sedimentary processes in controlling continental margin sedimentary cycles. The expedition recovered sediments from the Eocene to recent period, with a particular focus on the sequence stratigraphy of the late Miocene to recent, when global sea level change was dominated by glacioeustasy. Drilling in the Canterbury Basin, on the eastern margin of the South Island of New Zealand, takes advantage of high rates of Neogene sediment supply, which preserves a high-frequency (0.1–0.5 m.y.) record of depositional cyclicity. The Canterbury Basin provides an opportunity to study the complex interactions between processes responsible for the preserved stratigraphic record of sequences because of the proximity of an uplifting mountain chain, the Southern Alps, and strong ocean currents. Currents have locally built large, elongate sediment drifts within the prograding Neogene section. Expedition 317 did not drill into one of these elongate drifts, but currents are inferred to have strongly influenced deposition across the basin, including in locations lacking prominent mounded drifts. Upper Miocene to recent sedimentary sequences were cored in a transect of three sites on the continental shelf (landward to basinward, Sites U1353, U1354, and U1351) and one on the continental slope (Site U1352). The transect provides a stratigraphic record of depositional cycles across the shallow-water environment most directly affected by relative sea level change. Lithologic boundaries, provisionally correlative with seismic sequence boundaries, have been identified in cores from each site and provide insights into the origins of seismically resolvable sequences. This record will be used to estimate the timing and amplitude of global sea level change and to document the sedimentary processes that operate during sequence formation. Sites U1353 and U1354 provide significant, double-cored, high-recovery sections through the Holocene and late Quaternary for high-resolution study of recent glacial cycles in a continental shelf setting. Continental slope Site U1352 represents a complete section from modern slope terrigenous sediment to hard Eocene limestone, with all the associated lithologic, biostratigraphic, physical, geochemical, and microbiological transitions. The site also provides a record of ocean circulation and fronts during the last ~35 m.y. The early Oligocene (~30 Ma) Marshall Paraconformity was the deepest drilling target of Expedition 317 and is hypothesized to represent intensified current erosion or nondeposition associated with the initiation of thermohaline circulation following the separation of Australian and Antarctica. Expedition 317 set a number of scientific ocean drilling records: (1) deepest hole drilled in a single expedition and second deepest hole in the history of scientific ocean drilling (Hole U1352C, 1927 m); (2) deepest hole and second deepest hole drilled by the R/V JOIDES Resolution on a continental shelf (Hole U1351B, 1030 m; Hole U1353B, 614 m); (3) shallowest water depth for a site drilled by the JOIDES Resolution for scientific purposes (Site U1353, 84.7 m water depth); and (4) deepest sample taken by scientific ocean drilling for microbiological studies (1925 m, Site U1352). Expedition 317 supplements previous drilling of sedimentary sequences for sequence stratigraphic and sea level objectives, particularly drilling on the New Jersey margin (Ocean Drilling Program [ODP] Legs 150, 150X, 174A, and 174AX and IODP Expedition 313) and in the Bahamas (ODP Leg 166), but includes an expanded Pliocene section. Completion of at least one transect across a geographically and tectonically distinct siliciclastic margin was the necessary next step in deciphering continental margin stratigraphy. Expedition 317 also complements ODP Leg 181, which focused on drift development in more distal parts of the Eastern New Zealand Oceanic Sedimentary System (ENZOSS).Integrated Ocean Drilling Program Management InternationalPublished2.2. Laboratorio di paleomagnetismorestricte