1,826 research outputs found

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

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    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

    Chromosome Segregation Is Biased by Kinetochore Size

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    Chromosome missegregation during mitosis or meiosis is a hallmark of cancer and the main cause of prenatal death in humans. The gain or loss of specific chromosomes is thought to be random, with cell viability being essentially determined by selection. Several established pathways including centrosome amplification, sister-chromatid cohesion defects, or a compromised spindle assembly checkpoint can lead to chromosome missegregation. However, how specific intrinsic features of the kinetochore—the critical chromosomal interface with spindle microtubules—impact chromosome segregation remains poorly understood. Here we used the unique cytological attributes of female Indian muntjac, the mammal with the lowest known chromosome number (2n = 6), to characterize and track individual chromosomes with distinct kinetochore size throughout mitosis. We show that centromere and kinetochore functional layers scale proportionally with centromere size. Measurement of intra-kinetochore distances, serial-section electron microscopy, and RNAi against key kinetochore proteins confirmed a standard structural and functional organization of the Indian muntjac kinetochores and revealed that microtubule binding capacity scales with kinetochore size. Surprisingly, we found that chromosome segregation in this species is not random. Chromosomes with larger kinetochores bi-oriented more efficiently and showed a 2-fold bias to congress to the equator in a motor-independent manner. Despite robust correction mechanisms during unperturbed mitosis, chromosomes with larger kinetochores were also strongly biased to establish erroneous merotelic attachments and missegregate during anaphase. This bias was impervious to the experimental attenuation of polar ejection forces on chromosome arms by RNAi against the chromokinesin Kif4a. Thus, kinetochore size is an important determinant of chromosome segregation fidelity

    Modelling agronomic properties of Technosols constructed with urban wastes

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    International audienceThe greening of urban and suburban areas requires large amounts of arable earth that is a non-renewable resource. However, concentration of population in cities leads to the production of high amounts of wastes and by-products that are nowadays partly recycled as a resource and quite systematically exported out of urban areas. To preserve natural soil resources, a strategy of waste recycling as fertile substitutes is proposed. Eleven wastes are selected for their environmental harmlessness and their contrasted physico-chemical properties for their potential use in pedological engineering. The aim is (i) to demonstrate the feasibility of the formulation of fertile substrates exclusively with wastes and (ii) to model their physico-chemical properties following various types, number and proportions of constitutive wastes. Twenty-five binary and ternary combinations are tested at different ratios for total carbon, Olsen available phosphorus, cation exchange capacity, water pH, water retention capacity and bulk density. Dose-response curves describe the variation of physico-chemical properties of mixtures depending on the type and ratio of selected wastes. If these mixtures mainly mimic natural soils, some of them present more extreme urban soil features, especially for pH and P Olsen. The fertility of the new substrates is modelled by multilinear regressions for the main soil properties

    Association Of G-Quadruplex Forming Sequences With Human MtDNA Deletion Breakpoints

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    Background: Mitochondrial DNA (mtDNA) deletions cause disease and accumulate during aging, yet our understanding of the molecular mechanisms underlying their formation remains rudimentary. Guanine-quadruplex (GQ) DNA structures are associated with nuclear DNA instability in cancer; recent evidence indicates they can also form in mitochondrial nucleic acids, suggesting that these non-B DNA structures could be associated with mtDNA deletions. Currently, the multiple types of GQ sequences and their association with human mtDNA stability are unknown. Results: Here, we show an association between human mtDNA deletion breakpoint locations (sites where DNA ends rejoin after deletion of a section) and sequences with G-quadruplex forming potential (QFP), and establish the ability of selected sequences to form GQ in vitro. QFP contain four runs of either two or three consecutive guanines (2G and 3G, respectively), and we identified four types of QFP for subsequent analysis: intrastrand 2G, intrastrand 3G, duplex derived interstrand (ddi) 2G, and ddi 3G QFP sequences. We analyzed the position of each motif set relative to either 5\u27 or 3\u27 unique mtDNA deletion breakpoints, and found that intrastrand QFP sequences, but not ddi QFP sequences, showed significant association with mtDNA deletion breakpoint locations. Moreover, a large proportion of these QFP sequences occur at smaller distances to breakpoints relative to distribution-matched controls. The positive association of 2G QFP sequences persisted when breakpoints were divided into clinical subgroups. We tested in vitro GQ formation of representative mtDNA sequences containing these 2G QFP sequences and detected robust GQ structures by UV–VIS and CD spectroscopy. Notably, the most frequent deletion breakpoints, including those of the common deletion , are bounded by 2G QFP sequence motifs. Conclusions: The potential for GQ to influence mitochondrial genome stability supports a high-priority investigation of these structures and their regulation in normal and pathological mitochondrial biology. These findings emphasize the potential importance of helicases that subsequently resolve GQ to maintain the stability of the mitochondrial genome

    Impacto del uso de un cemento de bajo carbono en la mejora de la sostenibilidad de la producción de cemento

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    A preliminary assessment of conditions for the industrial manufacture of a new cementitious system based on clinker-calcined clay and limestone, developed by the authors, referred as “low carbon cement” is presented. The new cement enables the substitution of more than 50% of the mass of clinker without compromising performance. The paper presents the follow-up of an industrial trial carried out in Cuba to produce 130 tonnes of the new cement at a cement plant. The new material proved to fulfill national standards in applications such as the manufacture of hollow concrete blocks and precast concrete. No major differences either in the rheological or mechanical properties were found when compared with Portland cement. Environmental assessment of the ternary cement was made, which included comparison with other blended cements produced industrially in Cuba. The new cement has proven to contribute to the reduction of above 30% of carbon emissions on cement manufacture.Se presenta la evaluación preliminar de las condiciones de fabricación industrial de un nuevo sistema cementicio a partir del empleo de clínquer; arcillas calcinadas y piedra caliza; desarrollado por los autores; denominado “cemento de bajo carbono”. El nuevo cemento posibilita la reducción de más de un 50% de la masa de clínquer; sin comprometer el comportamiento del material. El presente trabajo presenta el monitoreo de la producción industrial en una planta en Cuba; de 130 t del nuevo cemento. El cemento obtenido cumple con las regulaciones nacionales de calidad y su empleo tiene similar rendimiento que el cemento Pórtland para la producción de bloques y hormigón de 25 MPa. Se realiza el análisis de impacto ambiental del cemento ternario mediante la comparación con otros cementos producidos industrialmente. El nuevo cemento puede contribuir a la reducción de más del 30% de las emisiones de CO2 asociadas a la manufactura de cemento

    An Economic Comparison between Alternative Rice Farming Systems in Tanzania Using a Monte Carlo Simulation Approach

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    Tanzania is the second-largest producer of rice (Oryza sativa) in Eastern, Central, and Southern Africa after Madagascar. Unfortunately, the sector has been performing poorly due to many constraints, including poor agricultural practices and climate variability. In addressing the challenge, the government is making substantial investments to speed the agriculture transformation into a more modernized, commercial, and highly productive and profitable sector. Our objective was to apply a Monte Carlo simulation approach to assess the economic feasibility of alternative rice farming systems operating in Tanzania while considering risk analysis for decision-makers with different risk preferences to make better management decisions. The rice farming systems in this study comprise rice farms using traditional practices and those using some or all of the recommended system of rice intensification (SRI) practices. The overall results show 2% and zero probability of net cash income (NCI) being negative for partial and full SRI adopters, respectively. Meanwhile, farmers using local and improved seeds have 66% and 60% probability of NCI being negative, correspondingly. Rice farms which applied fertilizers in addition to improved seeds have a 21% probability of negative returns. Additionally, net income for rice farms using local seeds was slightly worthwhile when the transaction made during the harvesting period compared to farms applied improved varieties due to a relatively high price for local seeds. These results help to inform policymakers and agencies promoting food security and eradication of poverty on the benefits of encouraging improved rice farming practices in the country. Despite climate variability, in Tanzania, it is still possible for rice farmers to increase food production and income through the application of improved technologies, particularly SRI management practices, which have shown a promising future.Peer Reviewe

    Adenovirus Infection in a Kidney–Pancreatic Transplant Recipient: Case Report

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    Adenovirus infection in transplant recipients may present from asymptomatic viremia to multisystemic involvement. Most frequently, it occurs in the first year after a kidney transplant, and it is secondary to the reactivation of latent disease. However, primary infection may occur, and disseminated disease is more common when related to primary infection. Kidney involvement may be confirmed by biopsy, although diagnosis may be presumptive. Reduction of immunosuppression and supportive care are important components of therapy. CASE DESCRIPTION: A 41-year-old female renal-pancreatic recipient 12 years before with chronic renal graft dysfunction and a functional pancreatic graft had a history of cytomegalovirus and polyoma virus infection 2 years after transplantation. She was taking tacrolimus, mycophenolate mofetil, and prednisolone. The patient was admitted after persistent uncharacteristic diarrhea 3 weeks before hospitalization without any relevant epidemiologic context. She was dehydrated, and the lab results showed worsened kidney function and leucocytosis. The viral culture revealed adenovirus. Vigorous hydration was implemented, and the mycophenolate mofetil dose was reduced. The patient was discharged, and renal function returned to previous values. DISCUSSION AND CONCLUSION: Adenovirus infection has a wide clinical presentation, and multisystemic involvement may occur in transplant recipients. Supportive care is paramount. The clinical features and viral culture confirm the diagnosis, although tissue samples and quantitative polymerase chain reaction may be required in more severe cases.info:eu-repo/semantics/publishedVersio

    Impact of integrase inhibitors on cardiovascular disease events in people with HIV starting antiretroviral therapy.

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    BACKGROUND Integrase strand transfer inhibitors (INSTI) have been associated with an increased risk for cardiovascular disease (CVD) events. We investigated the impact of starting INSTI-based antiretroviral therapy (ART) on CVD events among treatment-naïve people with HIV (PWH) using a target trial framework, which reduces the potential for confounding and selection bias. METHODS We included Swiss HIV Cohort Study participants who were ART-naïve after 05/2008, when INSTI became available in Switzerland. Individuals were categorized according to their first ART regimen (INSTI vs. other ART) and were followed from ART start until the first of CVD event (myocardial infarction, stroke, or invasive cardiovascular procedure), loss to follow-up, death, or last cohort visit. We calculated hazard ratios and risk differences using pooled logistic regression models with inverse probability of treatment and censoring weights. RESULTS Of 5362 participants (median age 38 years, 21% women, 15% of African origin), 1837 (34.3%) started INSTI-based ART, and 3525 (65.7%) started other ART. Within 4.9 years (IQR 2.4-7.4), 116 CVD events occurred. Starting INSTI-based ART was not associated with an increase in CVD events (adjusted hazard ratio 0.80, 95% confidence interval [CI] 0.46-1.39). Adjusted risk differences between individuals who started INSTI and those who started other ART were -0.17% (95% CI -0.37-0.19) after one year, -0.61% (-1.54-0.22) after 5 years, and -0.71% (-2.16-0.94) after 8 years. CONCLUSIONS In this target trial emulation, we found no difference in short or longer term risk for CVD events between treatment-naïve PWH who started INSTI-based and those on other ART

    The antiapoptotic effect of granulocyte colony-stimulating factor reduces infarct size and prevents heart failure development in rats

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    Background/Aim. Granulocyte colony-stimulating factor (G-CSF) reduces myocardial injury and improves cardiac function after myocardial infarction (MI). We investigated the early alterations provided by G-CSF and the chronic repercussions in infarcted rats. Methods. Male Wistar rats (200-250g) received vehicle (MI) or G-CSF (MI-GCSF) (50 mu g/kg, sc) at 7, 3 and 1 days before MI surgery. Afterwards MI was produced and infarct size was measured 1 and 15 days after surgery. Expression of anti-and proapoptotic proteins was evaluated immediately before surgery. 24 hours after surgery, apoptotic nuclei were evaluated. Two weeks after MI, left ventricular (LV) function was evaluated, followed by in situ LV diastolic pressure-volume evaluation. Results. Infarct size was decreased by 1 day pretreatment before occlusion (36 +/- 2.8 vs. 44 +/- 2.1% in MI; P<0.05) and remained reduced at 15 days after infarction (28 +/- 2.2 vs. 36 +/- 1.4% in MI; P<0.05). G-CSF pretreatment increased Bcl-2 and Bcl-xL protein expression, but did not alter Bax in LV. Apoptotic nuclei were reduced by treatment (Sham: 0.46 +/- 0.42, MI: 15.5 +/- 2.43, MI-GCSF: 5.34 +/- 3.34%; P<0.05). Fifteen days after MI, cardiac function remained preserved in G-CSF pretreated rats. The LV dilation was reduced in MI-G-CSF group as compared to MI rats, being closely associated with infarct size. Conclusion. The early beneficial effects of G-CSF were essentials to preserve cardiac function at a chronic stage of myocardial infarction2813340CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPsem informaçã
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