AnGeLi: A Tool for the Analysis of Gene Lists from Fission Yeast

Genome-wide assays and screens typically result in large lists of genes or proteins. Enrichments of functional or other biological properties within such lists can provide valuable insights and testable hypotheses. To systematically detect these enrichments can be challenging and time-consuming, because relevant data to compare against query gene lists are spread over many different sources. We have developed AnGeLi (Analysis of Gene Lists), an intuitive, integrated web-tool for comprehensive and customized interrogation of gene lists from the fission yeast, Schizosaccharomyces pombe. AnGeLi searches for significant enrichments among multiple qualitative and quantitative information sources, including gene and phenotype ontologies, genetic and protein interactions, numerous features of genes, transcripts, translation, and proteins such as copy numbers, chromosomal positions, genetic diversity, RNA polymerase II and ribosome occupancy, localization, conservation, half-lives, domains, and molecular weight among others, as well as diverse sets of genes that are co-regulated or lead to the same phenotypes when mutated. AnGeLi uses robust statistics which can be tailored to specific needs. It also provides the option to upload user-defined gene sets to compare against the query list. Through an integrated data submission form, AnGeLi encourages the community to contribute additional curated gene lists to further increase the usefulness of this resource and to get the most from the ever increasing large-scale experiments. AnGeLi offers a rigorous yet flexible statistical analysis platform for rich insights into functional enrichments and biological context for query gene lists, thus providing a powerful exploratory tool through which S. pombe researchers can uncover fresh perspectives and unexpected connections from genomic data. AnGeLi is freely available at: www.bahlerlab.info/AnGeLi

Primary thermometry in the intermediate Coulomb blockade regime

We investigate Coulomb blockade thermometers (CBT) in an intermediate temperature regime, where measurements with enhanced accuracy are possible due to the increased magnitude of the differential conductance dip. Previous theoretical results show that corrections to the half width and to the depth of the measured conductance dip of a sensor are needed, when leaving the regime of weak Coulomb blockade towards lower temperatures. In the present work, we demonstrate experimentally that the temperature range of a CBT sensor can be extended by employing these corrections without compromising the primary nature or the accuracy of the thermometer.Comment: 8 pages, 4 figure

Parallel Evaluation of Multi-join Queries

A number of execution strategies for parallel evaluation of multi-join queries have been proposed in the literature. In this paper we give a comparative performance evaluation of four execution strategies by implementing all of them on the same parallel database system, PRISMA/DB. Experiments have been done up to 80 processors. These strategies, coming from the literature, are named: Sequential Parallel, Synchronous Execution, Segmented Right-Deep, and Full Parallel. Based on the experiments clear guidelines are given when to use which strategy. This is an extended abstract; the full paper appeared in Proc. ACM SIGMOD'94, Minneapolis, Minnesota, May 24–27, 199

Novel Cascaded Ultra Bright Pulsed Source of Polarization Entangled Photons

A new ultra bright pulsed source of polarization entangled photons has been realized using type-II phase matching in spontaneous parametric down conversion process in two cascaded crystals. The optical axes of the crystals are aligned in such a way that the extraordinarily (ordinarily) polarized cone from one crystal overlaps with the ordinarily (extraordinarily) polarized cone from the second crystal. This spatial overlapping removes the association between the polarization and the output angle of the photons that exist in a single type-II down conversion process. Hence, entanglement of photons originating from any point on the output cones is possible if a suitable optical delay line is used. This delay line is particularly simple and easy to implement.Comment: 8 pages 8 figure

Cdk9 and H2Bub1 signal to Clr6-CII/Rpd3S to suppress aberrant antisense transcription

Mono-ubiquitylation of histone H2B (H2Bub1) and phosphorylation of elongation factor Spt5 by cyclin-dependent kinase 9 (Cdk9) occur during transcription by RNA polymerase II (RNAPII), and are mutually dependent in fission yeast. It remained unclear whether Cdk9 and H2Bub1 cooperate to regulate the expression of individual genes. Here, we show that Cdk9 inhibition or H2Bub1 loss induces intragenic antisense transcription of ∼10% of fission yeast genes, with each perturbation affecting largely distinct subsets; ablation of both pathways de-represses antisense transcription of over half the genome. H2Bub1 and phospho-Spt5 have similar genome-wide distributions; both modifications are enriched, and directly proportional to each other, in coding regions, and decrease abruptly around the cleavage and polyadenylation signal (CPS). Cdk9-dependence of antisense suppression at specific genes correlates with high H2Bub1 occupancy, and with promoter-proximal RNAPII pausing. Genetic interactions link Cdk9, H2Bub1 and the histone deacetylase Clr6-CII, while combined Cdk9 inhibition and H2Bub1 loss impair Clr6-CII recruitment to chromatin and lead to decreased occupancy and increased acetylation of histones within gene coding regions. These results uncover novel interactions between co-transcriptional histone modification pathways, which link regulation of RNAPII transcription elongation to suppression of aberrant initiation

Management of Acute Pancreatitis in the Pediatric Population: A Clinical Report From the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition Pancreas Committee

BACKGROUND:Although the incidence of acute pancreatitis (AP) in children is increasing, management recommendations rely on adult published guidelines. Pediatric-specific recommendations are needed. METHODS:The North American Society for Pediatric Gastroenterology, Hepatology and Nutrition Pancreas committee performed a MEDLINE review using several preselected key terms relating to management considerations in adult and pediatric AP. The literature was summarized, quality of evidence reviewed, and statements of recommendations developed. The authorship met to discuss the evidence, statements, and voted on recommendations. A consensus of at least 75% was required to approve a recommendation. RESULTS:The diagnosis of pediatric AP should follow the published INternational Study Group of Pediatric Pancreatitis: In Search for a CuRE definitions (by meeting at least 2 out of 3 criteria: (1) abdominal pain compatible with AP, (2) serum amylase and/or lipase values ≥3 times upper limits of normal, (3) imaging findings consistent with AP). Adequate fluid resuscitation with crystalloid appears key especially within the first 24 hours. Analgesia may include opioid medications when opioid-sparing measures are inadequate. Pulmonary, cardiovascular, and renal status should be closely monitored particularly within the first 48 hours. Enteral nutrition should be started as early as tolerated, whether through oral, gastric, or jejunal route. Little evidence supports the use of prophylactic antibiotics, antioxidants, probiotics, and protease inhibitors. Esophago-gastro-duodenoscopy, endoscopic retrograde cholangiopancreatography, and endoscopic ultrasonography have limited roles in diagnosis and management. Children should be carefully followed for development of early or late complications and recurrent attacks of AP. CONCLUSIONS:This clinical report represents the first English-language recommendations for the management of pediatric AP. Future aims should include prospective multicenter pediatric studies to further validate these recommendations and optimize care for children with AP

Association of Primary Care Physician Supply with Population Mortality in the United States, 2005-2015

Importance: Recent US health care reforms incentivize improved population health outcomes and primary care functions. It remains unclear how much improving primary care physician supply can improve population health, independent of other health care and socioeconomic factors. Objectives: To identify primary care physician supply changes across US counties from 2005-2015 and associations between such changes and population mortality. Design, Setting, and Participants: This epidemiological study evaluated US population data and individual-level claims data linked to mortality from 2005 to 2015 against changes in primary care and specialist physician supply from 2005 to 2015. Data from 3142 US counties, 7144 primary care service areas, and 306 hospital referral regions were used to investigate the association of primary care physician supply with changes in life expectancy and cause-specific mortality after adjustment for health care, demographic, socioeconomic, and behavioral covariates. Analysis was performed from March to July 2018. Main Outcomes and Measures: Age-standardized life expectancy, cause-specific mortality, and restricted mean survival time. Results: Primary care physician supply increased from 196014 physicians in 2005 to 204419 in 2015. Owing to disproportionate losses of primary care physicians in some counties and population increases, the mean (SD) density of primary care physicians relative to population size decreased from 46.6 per 100000 population (95% CI, 0.0-114.6 per 100000 population) to 41.4 per 100000 population (95% CI, 0.0-108.6 per 100000 population), with greater losses in rural areas. In adjusted mixed-effects regressions, every 10 additional primary care physicians per 100000 population was associated with a 51.5-day increase in life expectancy (95% CI, 29.5-73.5 days; 0.2% increase), whereas an increase in 10 specialist physicians per 100000 population corresponded to a 19.2-day increase (95% CI, 7.0-31.3 days). A total of 10 additional primary care physicians per 100000 population was associated with reduced cardiovascular, cancer, and respiratory mortality by 0.9% to 1.4%. Analyses at different geographic levels, using instrumental variable regressions, or at the individual level found similar benefits associated with primary care supply. Conclusions and Relevance: Greater primary care physician supply was associated with lower mortality, but per capita supply decreased between 2005 and 2015. Programs to explicitly direct more resources to primary care physician supply may be important for population health

Quantum interference with beamlike type-II spontaneous parametric down-conversion

We implement experimentally a method to generate photon-number$-$path and polarization entangled photon pairs using ``beamlike'' type-II spontaneous parametric down-conversion (SPDC), in which the signal-idler photon pairs are emitted as two separate circular beams with small emission angles rather than as two diverging cones.Comment: 4 pages, two-colum

Loss of circadian rhythm of blood pressure following acute stroke

BACKGROUND: Epidemiology of acute stroke in developing countries differs from that in the developed world, for example, the age at stroke, risk factors, subtypes of stroke and prognosis. Hypertension remains a dominant risk factor and prognostic indicator in patients with stroke in all communities. The risk of stroke is directly related to elevations of blood pressure. A number of clinical studies have shown that the control of hypertension leads to a reduction in the incidence of stroke in a community. However there is still considerable controversy surrounds the changes in blood pressure in various subtypes of strokes and problem of management of elevated BP after stroke. We studied the circadian rhythm of blood pressure in patients following acute stroke. METHODS: To study the circadian rhythm of blood pressure, fifty consecutive patients with an acute stroke who were admitted to medical emergency within 120 hours of onset were included in the study. After a detailed history and clinical examination, a continuous blood pressure monitor (Spacelab 90207) was attached on the side ipsilateral to intracranial lesion (unaffected arm). The blood pressure was recorded for 24 hours at 15 minutes interval during daytime (6.00 am–6.00 pm) and 20 minutes interval overnight (6 pm to 6 am). RESULTS: Risk factors for stroke in 50 patients included hypertension in 31(62%), diabetes mellitus in 4 (8%), smoking in 13 (26%) and previous history of transient ischemic attack in 7 (14%) patients. Mean systolic pressure and diastolic pressure at admission were higher in patients with hemorrhagic stroke -29 patients (177 ± 24 mmHg and 105 ± 19 mmHg respectively) compared to patients with ischemic strokes-21 patients (150 ± 36 mm Hg and 89 ± 18 mm Hg respectively, p value <0.01 in both comparisons). The normal diurnal variation in blood pressure (night time dipping of more than 10%) was abolished in 44 (88%) of patients. Out of 44 nondippers, 29 patients showed reverse dipping i.e. rise of BP during night time compared to day time levels. None of the risk factors, clinical or laboratory variables, type of stroke or blood pressure changes differed significantly between these two groups. CONCLUSIONS: Therefore, we showed a pathologically reduced or abolished circadian BP variation after stroke. Absence of normal dipping results in a higher 24 hour blood pressure load and may have more target organ damage than those with normal diurnal variation of blood pressure

Short and soft: multi-domain organization, tunable dynamics and jamming in suspensions of grafted colloidal cylinders with small aspect ratio

The yet virtually unexplored class of soft colloidal rods with small aspect ratio is investigated and shown to exhibit a very rich phase and dynamic behavior, spanning from liquid to nearly melt state. Instead of nematic order, these short and soft nanocylinders alter their organization with increasing concentration from isotropic liquid with random orientation to one with preferred local orientation and eventually a multi-domain arrangement with local orientational order. The latter gives rise to a kinetically suppressed state akin to structural glass with detectable terminal relaxation, which, on increasing concentration reveals features of hexagonally packed order as in ordered block copolymers. The respective dynamic response comprises four regimes, all above the overlapping concentration of 0.02 g/ml: I) from 0.03 to 0.1 g/mol the system undergoes a liquid-to-solid like transition with a structural relaxation time that grows by four orders of magnitude. II) from 0.1 to 0.2 g/ml a dramatic slowing-down is observed and is accompanied by an evolution from isotropic to multi-domain structure. III) between 0.2 and 0.6 g/mol the suspensions exhibit signatures of shell interpenetration and jamming, with the colloidal plateau modulus depending linearly on concentration. IV) at 0.74 g/ml in the densely jammed state, the viscoelastic signature of hexagonally packed cylinders from microphase-separated block copolymers is detected. These properties set short and soft nanocylinders apart from long colloidal rods (with large aspect ratio) and provide insights for fundamentally understanding the physics in this intermediate soft colloidal regime, as well as and for tailoring the flow properties of non-spherical soft colloids