Exploiting Monotone Convergence Functions in Parallel Programs

Scientific codes which use iterative methods are often difficult to parallelize well. Such codes usually contain \code{while} loops which iterate until they converge upon the solution. Problems arise since the number of iterations cannot be determined at compile time, and tests for termination usually require a global reduction and an associated barrier. We present a method which allows us avoid performing global barriers and exploit pipelined parallelism when processors can detect non-convergence from local information. (Also cross-referenced as UMIACS-TR-96-31.1

Transitive Closure of Infinite Graphs and its Applications

Integer tuple relations can concisely summarize many types of information gathered from analysis of scientific codes. For example they can be used to precisely describe which iterations of a statement are data dependent of which other iterations. It is generally not possible to represent these tuple relations by enumerating the related pairs of tuples. For example, it is impossible to enumerate the related pairs of tuples in the relation {[i] -> [i+2] | 1 <= i <= n-2}. Even when it is possible to enumerate the related pairs of tuples, such as for the relation {[i,j] -> [i',j'] | 1 <= i,j,i',j' <= 100}, it is often not practical to do so. We instead use a closed form description by specifying a predicate consisting of affine constraints on the related pairs of tuples. As we just saw, these affine constraints can be parameterized, so what we are really describing are infinite families of relations (or graphs). Many of our applications of tuple relations rely heavily on an operation called transitive closure. Computing the transitive closure of these "infinite graphs" is very different from the traditional problem of computing the transitive closure of a graph whose edges can be enumerated. For example, the transitive closure of the first relation above is the relation {[i] -> [i'] | exists beta s.t. i'-i = 2beta and 1 <= i <= i' <= n}. As we will prove, this computation is not computable in the general case. We have developed algorithms that produce exact results in most commonly occurring cases and produce upper or lower bounds (as necessary) in the other cases. This paper will describe our algorithms for computing transitive closure and some of its applications such as determining which inter-processor synchronizations are redundant. (Also cross-referenced as UMIACS-TR-95-48

Empleo de microtubérculos de papa cv. `Andinita' obtenidos en Sistemas de Inmersión temporal para producir minitubérculos en casa de cultivo

The potato (Solanum tuberosum L.) is one of the most important crops worldwide. Production of microtubers in temporary immersion systems represents a qualitative advance in obtaining planting material. This study aimed to determine the feasibility of using potato microtubers obtained in SIT to produce minitubers in greenhouse. One hundred microtubers were planted per treatment at a distance of 5.0 x 10 cm. After 15 days, the number of live plants was quantified, while, at 70 and 120 days of culture 15 plants were selected for treatment and fresh and dry mass of foliage and root was determined. In addition, other morphological variables at 120 days were evaluated. Survival ranged between 84 and 86%. The results showed that microtubers of cv. `Andinita' obtained in SIT can be used at greenhouse to produce minitubers. The immersion frequency with which they were obtained influenced the number of minitubers per plant as well as its content of dry mass. The best results were achieved with immersion every 4h. In this treatment 5.9 minituber were obtained per plant and 70.3% of these were in the category of 10.0 to 40.0g. Key words: minitubers, potato, seedLa papa (Solanum tuberosum L.), es uno de los cultivos más importantes a nivel mundial. La producción de microtubérculos en sistemas de inmersión temporal representa un salto cualitativo en la obtención de material vegetal de plantación. El presente trabajo tuvo como objetivo determinar la factibilidad del uso de microtubérculos de papa obtenidos en SIT para producir minitubérculos en casa de cultivo. Se plantaron 100 microtubérculos por tratamiento a una distancia de 5.0 x 10 cm. A los 15 días se cuantificó el número de plantas vivas, mientras que, a los 70 y 120 días de cultivo se seleccionaron 15 plantas por tratamiento y se determinó la masa fresca y seca tanto al follaje como a las raíces. Además, se evaluaron otras variables morfológicas a los 120 días. La supervivencia osciló entre 84 y 86%. Los resultados demostraron que microtubérculos de cv. `Andinita' obtenidos en SIT pueden emplearse en casa de cultivo para producir minitubérculos. La frecuencia de inmersión con que fueron obtenidos influyó sobre el número de minitubérculos por planta así como en su contenido de masa seca. Los mejores resultados se alcanzaron con los sometidos a inmersiones cada 4h. Con estos se obtuvieron 5.9 tubérculos por planta y el 70.3% se encontraba en la categoría de 10.0 a 40.0 g. Palabras clave: minitubérculos, papa, semill

Caracterización morfo-agronómica de plantas de papa cv. `Andinita' a partir de la siembra en campo de microtubérculos obtenidos en sistemas de inmersión temporal

The potato (Solanum tuberosum L.) is one of the most important crops worldwide. Use microtubers as planting material could mean a breakthrough for seed production programs. This study aimed to determine the morphological characteristics and field agronomic response of potato plants cv. `Andinita' obtained from microtubers of different diameters and fresh mass produced in temporary immersion systems. The microtubers were classified in four diameters, 4.0 mm, of 4.0 - 6.9 mm, of 7.0 - 10 mm and 10 mm and stored in plastic containers at a temperature ranging between 11.0 and 15.0°C. At the time of planting was observed the microtubers with a diameter less than 4.0 mm were dehydrated and therefore were not used. At 21 days of the plantation differences in the survival of plants were significant, the highest percentage (93.9%) was achieved by planting microtubers with more than 10 mm diameter. Microtubers obtaining in temporary immersion systems did not affect the morphological characteristics of the plants during their growth cycle and from the point of view agricultural an average of 8.5 at 9.5 tubers by plant was achieved. With a relative yield per plant between 1.9 - 2.3 kg and 16 to 23% of tubers with desired characteristics for conservation as seed. It was shown that both the vegetative development of the plantation as the number and fresh weight of tubers obtained depended on the size and fresh weight of microtubers used as planting material and that may use them for direct planting in the field. Key words: microtubers, seed, Solanum tuberosum subsp. andigenumLa papa (Solanum tuberosum L.), es uno de los cultivos más importantes a nivel mundial. Utilizar microtubérculos como material vegetal de plantación podría significar un importante avance para los programas de producción de semilla. El presente trabajo tuvo como objetivos determinar en campo las características morfológicas y la respuesta agronómica de plantas de papa cv. `Andinita' obtenidas de microtubérculos de diferentes diámetros y masa fresca producidos en sistemas de inmersión temporal. Los microtubérculos fueron clasificados en cuatro diametros, 4.0 mm, de 4.0 6.9 mm, de 7.0 10 mm y 10 mm y se conservaron en contenedores plásticos a una temperatura que osciló entre 11.0 y 15.0°C. Al momento de la siembra se observó que los microtubérculos con un diámetro inferior a 4.0 mm se habían deshidratado y por lo tanto no fueron utilizados. A los 21 días de realizada la plantación existían diferencias significativas en la supervivencia de las plantas, el mayor porcentaje (93.9%) se alcanzó al plantar microtubérculos con un diámetro superior a 10 mm. La obtención de los microtubérculos en sistemas de inmersión temporal no afectó las características morfológicas de las plantas durante su ciclo vegetativo y desde el punto de vista agronómico se logró un promedio de 8.5 a 9.5 tubérculos por planta. Con un rendimiento relativo por planta entre 1.9 - 2.3 kg y de 16 a 23% de tubérculos con características deseadas para su conservación como semilla. Se demostró que tanto el desarrollo vegetativo de la plantación como el número y masa fresca de los tubérculos obtenidos, dependió del diámetro y la masa fresca de los microtubérculos utilizados como material vegetal de plantación y que es posible utilizarlos para su siembra directa en campo. Palabras clave: microtubérculos, Solanum tuberosum subsp. andigenum, semill

Efecto del tipo de explante y la frecuencia de inmersión en la producción de microtubérculos de papa cv. `Andinita' en Sistemas de Inmersión Temporal

The potato (Solanum tuberosum L.) is one of the most important crops. Commercial production of microtubers in temporary immersion systems could represent a qualitative step in the production of planting material. This study aimed to determine the effect of explant type and immersion frequency in the formation and development of microtubers of potato cv. `Andinita' in temporary immersion systems. The effect of three immersion frequencies (every 2, 3 and 4 h) and three types of explants (apical buds, first and second nodal segments) was evaluated. Each culture vessel was inoculated with 100 explants, for a total of nine treatments with three replicates each one. In all treatments with an immersion every 4 h were achieved best results with respect to height of the plants, whereas, by combining this immersion frequency and apical buds, was obtained the higher number of nodal segments per plant (10.5). In the tuberization stage over 88% of the microtubers obtained presented a diameter greater than 4.0 mm and a fresh mass that ranged between 0.5 and 3.5 g. It was shown that both the immersion frequency and the type of explant influenced the quality and number of microtubers produced. The best results were obtained with an immersion every 4 h and apical buds as initial explants with 4.9 microtubers per plant.Key words: apical buds, immersion frequency, seedLa papa (Solanum tuberosum L.) es uno de los cultivos más importantes. La producción comercial de microtubérculos en sistemas de inmersión temporal podría representar un salto cualitativo en la obtención de material vegetal de plantación. Este estudio tuvo como objetivos determinar el efecto del tipo de explante y la frecuencia de inmersión en la formación y desarrollo de microtubérculos de papa cv. `Andinita' en sistemas de inmersión temporal. Se evaluó el efecto de tres frecuencias de inmersión (cada 2, 3 y 4 h) y tres tipos de explante (yemas apicales, primer y segundo segmento nodal). Cada recipiente de cultivo se inoculó con 100 explantes, para un total de nueve tratamientos con tres repeticiones cada uno. En todos los tratamientos con una inmersión cada 4 h se alcanzaron los mejores resultados con respecto a la altura de las plantas, mientras que, al combinar esta frecuencia de inmersión con el uso de yemas apicales, se obtuvo el mayor número de segmentos nodales por planta (10.5). En la etapa de tuberización más del 88% de los microtubérculos obtenidos presentaron un diámetro superior a 4.0 mm y una masa fresca que osciló entre 0.5 y 3.5 g. Se demostró que tanto la frecuencia de inmersión, como el tipo de explante influyeron en la calidad y número de microtubérculos producidos. Los mejores resultados se obtuvieron con una inmersión cada 4 h y yemas apicales como explante inicial con 4.9 microtubérculos por planta. Palabras clave: frecuencia de inmersión, semilla, yemas apicale

PRIORITIZATION OF RESULTS FROM WHOLE EXOME SEQUENCING IN FAMILIAL INTRACRANIAL ANEURYSM

poster abstractWhole exome sequencing (WES) is an innovative approach to identifying rare variants associated with disease; however, reducing the large number of variants to a useful set of candidate genes is challenging. We developed a ranking system utilizing data from a previous genome-wide linkage analysis and various bioinformatics databases to prioritize the results of WES from families having multiple members with intracranial aneurysms. WES was performed in 35 affected individuals and 10 unaffected individ-uals across 7 families. All samples were genotyped (Illumina® OmniExpress) and sequenced (Agilent© SureSelect™ 50Mb Human All Exon Kit). Linkage analysis (Illumina 6K) was previously performed using autosomal domi-nant/recessive modes of inheritance. Application of quality filters resulted in 91,659 single nucleotide variants (SNVs). Nonsynonymous SNVs within an exon having an allele frequency of <3% were retained. Further filtering was performed based on Mendelian in-heritance (autosomal dominant or recessive). A ranking system prioritized retained variants based on the inheritance pattern specific to each family, occurrence in multiple families, relation to pathways and genes of interest, degree of penetrance, presence within a linkage peak, and whether the re-sultant proteins were predicted to be deleterious. Out of a 9-point score, 292 variants in 190 genes received scores of at least 5. Of these, 14 variants in 10 genes met the majority of prioritization criteria by achieving scores of over 7. While several WES studies have been successful at identifying genes im-portant to rare diseases, few have examined how to produce a list of candi-date genes contributing to a complex disease from WES data. We show that a ranking system that combines WES with bioinformatics resources and link-age data is a powerful approach to prioritize candidate genes for a complex disease like familial intracranial aneurysms. Subsequent studies are required to validate the utility of this approach

Whole-Exome Sequencing in Familial Parkinson Disease

IMPORTANCE: Parkinson disease (PD) is a progressive neurodegenerative disease for which susceptibility is linked to genetic and environmental risk factors. OBJECTIVE: To identify genetic variants contributing to disease risk in familial PD. DESIGN, SETTING, AND PARTICIPANTS: A 2-stage study design that included a discovery cohort of families with PD and a replication cohort of familial probands was used. In the discovery cohort, rare exonic variants that segregated in multiple affected individuals in a family and were predicted to be conserved or damaging were retained. Genes with retained variants were prioritized if expressed in the brain and located within PD-relevant pathways. Genes in which prioritized variants were observed in at least 4 families were selected as candidate genes for replication in the replication cohort. The setting was among individuals with familial PD enrolled from academic movement disorder specialty clinics across the United States. All participants had a family history of PD. MAIN OUTCOMES AND MEASURES: Identification of genes containing rare, likely deleterious, genetic variants in individuals with familial PD using a 2-stage exome sequencing study design. RESULTS: The 93 individuals from 32 families in the discovery cohort (49.5% [46 of 93] female) had a mean (SD) age at onset of 61.8 (10.0) years. The 49 individuals with familial PD in the replication cohort (32.6% [16 of 49] female) had a mean (SD) age at onset of 50.1 (15.7) years. Discovery cohort recruitment dates were 1999 to 2009, and replication cohort recruitment dates were 2003 to 2014. Data analysis dates were 2011 to 2015. Three genes containing a total of 13 rare and potentially damaging variants were prioritized in the discovery cohort. Two of these genes (TNK2 and TNR) also had rare variants that were predicted to be damaging in the replication cohort. All 9 variants identified in the 2 replicated genes in 12 families across the discovery and replication cohorts were confirmed via Sanger sequencing. CONCLUSIONS AND RELEVANCE: TNK2 and TNR harbored rare, likely deleterious, variants in individuals having familial PD, with similar findings in an independent cohort. To our knowledge, these genes have not been previously associated with PD, although they have been linked to critical neuronal functions. Further studies are required to confirm a potential role for these genes in the pathogenesis of PD

Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries

In the version of this article initially published, the author affiliations incorrectly listed “Candiolo Cancer Institute FPO-IRCCS, Candiolo (TO), Italy” as “Candiolo Cancer Institute, Candiolo, Italy.” The change has been made to the HTML and PDF versions of the article

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707