Miracle-dz/UniFAR-FTUs huggingface dataset:
NEMix: Single-cell Nested Effects Models for Probabilistic Pathway Stimulation

Nested effects models have been used successfully for learning subcellular networks from high-dimensional perturbation effects that result from RNA interference (RNAi) experiments. Here, we further develop the basic nested effects model using high-content single-cell imaging data from RNAi screens of cultured cells infected with human rhinovirus. RNAi screens with single-cell readouts are becoming increasingly common, and they often reveal high cell-to-cell variation. As a consequence of this cellular heterogeneity, knock-downs result in variable effects among cells and lead to weak average phenotypes on the cell population level. To address this confounding factor in network inference, we explicitly model the stimulation status of a signaling pathway in individual cells. We extend the framework of nested effects models to probabilistic combinatorial knock-downs and propose NEMix, a nested effects mixture model that accounts for unobserved pathway activation. We analyzed the identifiability of NEMix and developed a parameter inference scheme based on the Expectation Maximization algorithm. In an extensive simulation study, we show that NEMix improves learning of pathway structures over classical NEMs significantly in the presence of hidden pathway stimulation. We applied our model to single-cell imaging data from RNAi screens monitoring human rhinovirus infection, where limited infection efficiency of the assay results in uncertain pathway stimulation. Using a subset of genes with known interactions, we show that the inferred NEMix network has high accuracy and outperforms the classical nested effects model without hidden pathway activity. NEMix is implemented as part of the R/Bioconductor package ‘nem’ and available at www.cbg. ethz.ch/software/NEMix.
Aggrecan fragments as biomarkers in osteoarthritis

Background: In osteoarthritis (OA) the balance of cartilage matrix synthesis and degradation is disturbed, resulting in a gradual destruction of the articular cartilage. Matrix components released into body fluids by proteolytic cleavage can be used as biomarkers of ongoing processes. This thesis focuses on proteolytic degradation of the proteoglycan aggrecan with the overall aim to study the potential of aggrecan fragments as biomarkers in knee OA. Methodology/Principal findings: Using neoepitope specific antibodies in Western blots, aggrecan fragments were identified in knee cartilage and synovial fluid (SF) pooled from individuals with a wide spectrum of disease. Aggrecanases were found to dominate aggrecan proteolysis in disease, although a contribution of matrix metalloprotease (MMP) activity was noted. Western blot quantification in individual samples showed that the proportion of aggrecan released into SF generated by aggrecanases varied in disease, and was higher in diagnostic groups associated with high disease activity. Quantification by ELISA of SF ARGS showed that SF ARGS better distinguished samples from patients with knee joint disease from samples obtained from knee healthy individuals than aggrecan measures not specific for this neoepitope. In patients meniscectomized 18 years earlier, SF ARGS levels were inversely associated with progression of radiographic OA. Conclusions: Aggrecanase is the dominating protease in human knee OA and its activity toward the aggrecan interglobular domain (IGD) is elevated in disease. SF levels of aggrecan ARGS fragments generated by this IGD activity can be used as biomarkers and has diagnostic as well as prognostic capabilities.
Who Wants to Self-Track Anyway? Measuring the Relation between Self-Tracking Behavior and Personality Traits

We describe an empirical study of the usage of a mobility self-tracking app, SensibleJournal 2014, which provides personal mobility information to N=796 participants as part of a large mobile sensing study. Specifically, we report on the app design, as well as deployment, uptake and usage of the app. The latter analysis is based on logging of user interactions as well as answers gathered from a questionnaire provided to the participants. During the study enrollment process, participants were asked to fill out a questionnaire including a Big Five inventory and Narcissism NAR-Q personality tests. A comparison of personality traits was conducted to understand potential differences among the users and non-users of the app. We found a relation between self-tracking and conscientiousness, but contrary to the view in popular media, we found no relation between self-tracking behavior and narcissism.
Involvement of Arabidopsis HOS15 in histone deacetylation and cold tolerance

Histone modification in chromatin is one of the key control points in gene regulation in eukaryotic cells. Protein complexes composed of histone acetyltransferase or deacetylase, WD40 repeat protein, and many other components have been implicated in this process. Here, we report the identification and functional characterization of HOS15, a WD40-repeat protein crucial for repression of genes associated with abiotic stress tolerance through histone deacetylation in Arabidopsis. HOS15 shares high sequence similarity with human transducin-beta like protein (TBL), a component of a repressor protein complex involved in histone deacetylation. Mutation of the HOS15 gene renders mutant plants hypersensitive to freezing temperatures. HOS15 is localized in the nucleus and specifically interacts with histone H4. The level of acetylated histone H4 is higher in the hos15 mutant than in WT plants. Moreover, the stress inducible RD29A promoter is hyperinduced and associated with a substantially higher level of acetylated histone H4 in the hos15 mutant under cold stress conditions. Our results suggest a critical role for gene activation/repression by histone acetylation/deacetylation in plant acclimation and tolerance to cold stress.
Application of Pyrolysis and Gas Chromatography to Geochemical Characterization of Kerogen in Sedimentary Rock

Pyrolysis and gas chromatography are combined in a new technique which characterizes the kerogen in a sedimentary rock. This technique makes it possible to determine with very small quantities (50-100 mg) of rock material, such as drill cuttings, the origin of the organic matter and its degree of evolution. The technique was tested on a clay-bearing formation from North Africa which was very well defined both geologically and palynologically. The tests gave the following results: (1) low-temperature pyrolysis (250°C) of continental deposits yields degradation products which are rich in aromatics (benzene, toluene, xylene, cumene, etc.), whereas products rich in paraffinic hydrocarbons are derived from marine deposits; (2) the relative concentrations of light hydrocar ons in some samples indicate whether gas or oil has originated from a particular source rock; and (3) the evolution of the kerogen (which results in an increase in the C/H ratio) can be estimated from the nature of the degradation products and more especially from the degree of degradation of the kerogen at high temperatures. The results seem to be consistent with those obtained from parallel studies of the carbonization of spores and "organic microfossils" and the crystallization of clays.
First year of upper tropospheric integrated content of CO 2 from IASI hyperspectral infrared observations

Abstract. Simultaneous observations from the Infrared Atmospheric Sounding Interferometer (IASI) and from the Advanced Microwave Sounding Unit (AMSU), launched together onboard the European MetOp platform in October 2006, are used to retrieve an upper tropospheric content of carbon dioxide (CO2) covering the range 11–15 km (100–300 hPa), in clear-sky conditions, in the tropics, over sea, for the first year of operation of MetOp (January 2008–December 2008). With its very high spectral resolution, IASI provides fourteen channels in the 15 μm band highly sensitive to CO2 with reduced sensitivities to other atmospheric variables. IASI observations, sensitive to both CO2 and temperature, are used in conjunction with AMSU observations, only sensitive to temperature, to decorrelate both signals through a non-linear inference scheme based on neural networks. A key point of this approach is that no use is made of prior information in terms of CO2 seasonality, trend, or geographical patterns. The precision of the retrieval is estimated to be about 2.0 ppmv (~0.5%) for a 5°×5° spatial resolution on a monthly time scale. Features of the retrieved CO2 space-time distribution include: (1) a strong seasonal cycle of 4 ppmv in the northern tropics with a maximum in June–July and a minimum in September–October. This cycle is characterized by a backward two-months lag as compared to the surface, by a backward one-month lag as compared to measurements performed at 11 km, and by a forward one-month lag as compared to observations performed at the tropopause (16 km). This is likely due to the time-lag of CO2 cycle while transported from the surface to the upper troposphere; (2) a more complex seasonal cycle in the southern tropics, in agreement with in-situ measurements; (3) a latitudinal variation of CO2 shifting from a South-to-North increase of 3.5 ppmv in boreal spring to a South-to-North decrease of 1.5 ppmv in the fall, in excellent agreement with tropospheric aircraft measurements; (4) signatures of CO2 emissions transported to the upper troposphere. In addition to bringing an improved view of CO2 distribution, these results from IASI should provide an additional means to observe and understand atmospheric transport pathways of CO2 from the surface to the upper troposphere.
Intraluminal Flagellin Differentially Contributes to Gut Dysbiosis and Systemic Inflammation following Burn Injury

Burn injury is associated with a loss of gut barrier function, resulting in systemic dissemination of gut-derived bacteria and their products. The bacterial protein and TLR5 agonist, flagellin, induces non-specific innate immune responses. Because we detected flagellin in the serum of burn patients, we investigated whether gut-derived flagellin was a primary or secondary contributor to intestinal dysfunction and systemic inflammation following burn injury. The apical surface of polarized human intestinal epithelial cells (IECs), Caco-2BBe, were exposed to 50 or 500 ng of purified flagellin and 1 x 105 of an intestinal E. coli (EC) isolate as follows: 1) flagellin added 30 min prior to EC, 2) flagellin and EC added simultaneously, or 3) EC added 30 min prior to flagellin. Our results showed that luminal flagellin and EC modulated each other's biological actions, which influenced their ability to induce basolateral secretion of inflammatory cytokines and subsequent translocation of bacteria and their products. A low dose of flagellin accompanied by an enteric EC in the lumen, tempered inflammation in a dose- and time-dependent manner. However, higher doses of flagellin acted synergistically with EC to induce both intestinal and systemic inflammation that compromised barrier integrity, increasing systemic inflammation following burn injury, a process we have termed flagellemia. In a murine model of burn injury we found that oral gavage of flagellin (1 μg/mouse) significantly affected the gut microbiome after burn injury. In these mice, flagellin disseminated out of the intestine into the serum and to distal organs (mesenteric lymph nodes and lungs) where it induced secretion of monocyte chemoattractant protein (MCP-1) and CXCL1/KC (mouse equivalent of human IL-8) at 24 and 48h post-burn. Our results illustrated that gut-derived flagellin alone or accompanied by a non-pathogenic enteric EC strain can function as an initiator of luminal and systemic inflammation following burn injury.
Distributed under Creative Commons Cc-by 4.0 the Role of a Water Bug, Sigara Striata, in Freshwater Food Webs

Freshwater food webs are dominated by aquatic invertebrates whose trophic relationships are often poorly known. Here, I used laboratory experiments to study the role of a water bug, Sigara striata, as a potential predator and prey in food webs of stagnant waters. Multiple-choice predation experiment revealed that Sigara, which had been considered mostly herbivorous, also consumed larvae of Chironomus midges. Because they often occur in high densities and are among the most ubiquitous aquatic insects, Sigara water bugs may be important predators in fresh waters. A second experiment tested the role of Sigara as a potential prey for 13 common invertebrate predators. Mortality of Sigara inflicted by different predators varied widely, especially depending on body mass, foraging mode (ambush/searching) and feeding mode (chewing/suctorial) of the predators. Sigara was highly vulnerable to ambush predators, while searching predators caused on average 8.1 times lower mortality of Sigara. Additionally, suctorial predators consumed on average 6.6 times more Sigara individuals than chewing predators, which supports previous results hinting on potentially different predation pressures of these two types of predators on prey populations. The importance of these two foraging-related traits demonstrates the need to move from body mass based to multiple trait based descriptions of food web structure. Overall, the results suggests that detailed experimental studies of common but insufficiently known species can significantly enhance our understanding of food web structure.
The Uncertainty of an Assessment Procedure for the West Greenland Stock of Northern Shrimp, Pandalus borealis (Krøyer)

The shrimp (Pandalus borealis) resource off West Greenland was assessed by fitting, to four fleets operating over different periods, separate CPUE models, which were then combined. A logistic model of population dynamics was then fitted to this data and a standard trawl survey series. Uncertainty was estimated by a jack-knife procedure— leaving out one year's data at a time—in several forms: omitting data from all steps in the process or only from the last step of fitting the production model; or omitting data either for one year at a time at each point in the series or for a sequence of years at the start of the series. Initial results from jack-knifing the entire procedure gave a small scatter (CV 8%) in optimal fishing mortality, but the sustainable catch had a 13% CV and ranged from 9% lower to 52% higher than the value based on all the data. Omitting the first year's data created an outlier with a 47% lower sustainable fishing mortality. When jack-knifing only the input to the logistic population model, the optimal fishing mortality retained a CV of near 8%, but the CV of sustainable catch fell to about 4% (ranging from 8.5% lower to only 9.2% higher). Much of the variation in estimated sustainable catch therefore appeared due to uncertainty in the standardized CPUE series. However, omitting the first year's data continued to give an outlying point, so the effect of leaving out the first year's data was investigated further. When the experiment was repeated with the first two data points permanently omitted, the CV of MSY remained near 4%, but the variation in sustainable fishing mortality and in standing stock became large. Also, there was little difference whether the jack-knife procedure included the GLM fitting of the CPUE series or whether points were simply omitted from a single series based on all the years' data. I.e. particular properties of the data points appeared to have significant effects. The jack-knife procedure appears useful for examining the reliability of this standard method of fishery assessment, and these results indicate that the uncertainty of such results may be unpredictable, large, variable between model parameters, and difficult to assign to any particular step in the procedure. 1 Author to whom correspondence should be addressed, at: Norwegian College of Fishery Science, Dept. of Marine and Freshwater Biology, University of Tromsø, Breivika, 9037 Tromsø, Norway. Tlf +47 77 64 60 22; Fax: +47 77 64 60 20; carstenh@nfh.uit. no.
Factors Affecting Retweetability: An Event-Centric Analysis on Twitter

In Twitter information primarily propagates through retweet mechanism. While a massive amount of tweets gets generated everyday, only a handful of them get retweeted widely. In this study, we have investigated the impact of user-roles in retweet phenomena. We have introduced the concept of “Information Diffusion Impact” (IDI) and identified three important user roles, namely “information starter”, “amplifier”, and “transmitter”. Retweetability has been modeled using IDI impact for different user roles along with the content features like presence of hashtag, URL etc. Further, the effect of a major event on the factors affecting retweetability has been investigated. Our findings demonstrate that retweetability is significantly affected by amplifiers and informationstarters and these effects change substantially due to event. We have also reexamined our model in another dataset of the Boston marathon bomb blast, 2013 and the outcome of this analysis is in good agreement with our findings from Japan earthquake dataset.
Formation and variability of the South Pacific Sea Surface Salinity maximum in recent decades

This study investigates causes for the formation and variability of the Sea Surface Salinity maximum (SSS > 36) centered near 18°S-124°W in the South Pacific Ocean over the 1990-2011 period at the seasonal time scale and above. We use two monthly gridded products of SSS based on in situ measurements, high-resolution along-track Voluntary Observing Ships thermo-salinograph data, new SMOS satellite data, and a validated ocean general circulation model with no direct SSS relaxation. All products reveal a seasonal cycle of the location of the 36-isohaline barycenter of about ±400 km in longitude in response to changes in the South Pacific Convergence Zone location and Easterly winds intensity. They also show a low frequency westward shift of the barycenter of 1400 km from the mid 1990s to the early 2010s that could not be linked to the El Nino Southern Oscillation phenomena. In the model, the processes maintaining the 22 year equilibrium of the high salinity in the mixed layer are the surface forcing (˜+0.73 pss/yr), the horizontal salinity advection (˜-0.37 pss/yr), and processes occurring at the mixed layer base (˜-0.35 pss/yr).
Combinatorics, Probability and Computing the Maximum Degree of Series­parallel Graphs the Maximum Degree of Series-parallel Graphs

We prove that the maximum degree Δ n of a random series-parallel graph with n vertices satisfies Δ n / log n → c in probability, and E Δ n ∼ c log n for a computable constant c > 0. The same kind of result holds for 2-connected series-parallel graphs, for outerplanar graphs, and for 2-connected outerplanar graphs.
The frequency of the predominant Jewish mutations in BRCA1 and BRCA2 in unselected Ashkenazi colorectal cancer patients

It is presently unclear whether carriers of BRCA1 mutations have an increased risk for colorectal cancer (CRC). To gain insight into this issue, 225 unselected Ashkenazi Jewish CRC patients were tested for the presence of the three common Jewish BRCA1/2 germline mutations: 185delAG and 5382insC (BRCA1) and 6174delT (BRCA2). A total of four carriers was found (4/225, 1.78%). This frequency is similar to the estimated normal Ashkenazi population frequency, thus suggesting that these specific mutations do not contribute to CRC predisposition. © 2001 Cancer Research Campaign
Realizability and independence of premiss : a note

Independence of premiss is the axiom scheme ∀x[(¬A(x) → ∃yB(x, y)) → ∃y(¬A(x) → B(x, y))] The principle is underivable in HA, since it is inconsistent with ECT0. However, HA is closed under the derived rule: if HA ¬A → ∃yB(y), then HA ¬A → B(n), for some natural number n. A variation is the principle IP0: ∀x(Ax ∨ ¬Ax) ∧ (∀xAx → ∃yBy) → ∃y(∀xAx → By)
Combining Evidence of Preferential Gene-Tissue Relationships from Multiple Sources

An important challenge in drug discovery and disease prognosis is to predict genes that are preferentially expressed in one or a few tissues, i.e. showing a considerably higher expression in one tissue(s) compared to the others. Although several data sources and methods have been published explicitly for this purpose, they often disagree and it is not evident how to retrieve these genes and how to distinguish true biological findings from those that are due to choice-of-method and/or experimental settings. In this work we have developed a computational approach that combines results from multiple methods and datasets with the aim to eliminate method/study-specific biases and to improve the predictability of preferentially expressed human genes. A rule-based score is used to merge and assign support to the results. Five sets of genes with known tissue specificity were used for parameter pruning and cross-validation. In total we identify 3434 tissue-specific genes. We compare the genes of highest scores with the public databases: PaGenBase (microarray), TiGER (EST) and HPA (protein expression data). The results have 85% overlap to PaGenBase, 71% to TiGER and only 28% to HPA. 99% of our predictions have support from at least one of these databases. Our approach also performs better than any of the databases on identifying drug targets and biomarkers with known tissue-specificity.
Assessment of the Risk Level for Carp Welfare Based on the Water Quality in RAS

In this paper results of the risk level assessment of carp welfare (Cyprinus carpio) in recirculating aquaculture system (RAS) are presented. We used different quantitative nutrition levels (3% and 4% of feed) and examined changes of the water quality in tanks during first, second and third month of the experiment. The risk assessment is based on carp needs regarding optimal ranges of water temperature, dissolved oxygen (DO), and suggested upper level of unionized ammonia (NH3-N) content. According to the results, average values of the water temperature and DO were in optimal range. The average content of NH3-N was above recommended level. Water quality was deteriorated along with duration of experiment. In the first period i.e. first month of the experiment welfare risk in both groups is at the lowest level and the highest in the last period. The total score is higher in group fed with 4% of feed then in group which received 3% of feed.
An analysis of Marvel—A Nuclear Shock-Tube Experiment

Marvel, a nuclear-driven shock-tube experiment, consisted of a 2.2-kT nuclear explosive detonated 176 meters underground at one end of a 122-meter long, 1-meter diameter horizontal tunnel. Vaporization of material in the immediate vicinity of the explosive provided the source of high-energy driven gas. The driven gas was the ambient atmospheric air in the tunnel. Marvel was conducted as an experimental and calculational study of the time-dependent flow of energy in the tunnel and surrounding alluvium. This paper describes (1) the design of Marvel, (2) the dynamic and postshot experimental results, and (3) a numerical simulation of the experiment. Experimental and calculational results indicate the following. The high-energy air shock traveled down the tunnel nearly 50 times faster than the shock in the surrounding alluvium. Over the first 30 meters of the tunnel, the shock had a velocity of approximately Mach 380; during its 4-msec transit of the 122-meter tunnel, it attenuated to approximately Mach 30. Significant ablation of material from the tunnel walls had the primary effect in attenuating the air shock. The source energy was preferentially channeled down the tunnel, and a cone-shaped cavity resulted.