Miracle-dz/UniFAR-FTUs huggingface dataset:
Extending the Applicability of the Dose Addition Model to the Assessment of Chemical Mixtures of Partial Agonists by Using a Novel Toxic Unit Extrapolation Method

Dose addition, a commonly used concept in toxicology for the prediction of chemical mixture effects, cannot readily be applied to mixtures of partial agonists with differing maximal effects. Due to its mathematical features, effect levels that exceed the maximal effect of the least efficacious compound present in the mixture, cannot be calculated. This poses problems when dealing with mixtures likely to be encountered in realistic assessment situations where chemicals often show differing maximal effects. To overcome this limitation, we developed a pragmatic solution that extrapolates the toxic units of partial agonists to effect levels beyond their maximal efficacy. We extrapolated different additivity expectations that reflect theoretically possible extremes and validated this approach with a mixture of 21 estrogenic chemicals in the E-Screen. This assay measures the proliferation of human epithelial breast cancers. We found that the dose-response curves of the estrogenic agents exhibited widely varying shapes, slopes and maximal effects, which made it necessary to extrapolate mixture responses above 14% proliferation. Our toxic unit extrapolation approach predicted all mixture responses accurately. It extends the applicability of dose addition to combinations of agents with differing saturating effects and removes an important bottleneck that has severely hampered the use of dose addition in the past.
Specific Correlation between the Hegu Point (LI4) and the Orofacial Part: Evidence from an fMRI Study

Acupoint specificity is a foundational concept in acupuncture theory. It is closely related to the function of the acupoint. In this study, we sought to probe the central mechanisms of the specific correlation between LI4 and orofacial part in Bell's palsy patients. In total, 36 patients with left Bell's palsy were divided into three groups in random order, and each group received transcutaneous electrical acupoint stimulation (TEAS) at only one of three acupoints (LI4, ST6, and a sham point). A single-block fMRI design paradigm was applied to separately detect neural activity related to different stages of TEAS (prestimulation resting state, stimulation, and poststimulation resting state). Functional magnetic resonance imaging data were acquired during TEAS. There were extensive neuronal activities in the LI4 and ST6 groups and significant differences between stimulation at real and sham points. Brain regions were activated more by real acupoint TEAS than by sham point TEAS. Brain regions that were activated with LI4 and ST6 were broadly overlapping and adjacent. Our results provide supplementary neuroimaging evidence for the existence of acupoint specificity. These results may confirm the central mechanisms of the specific correlation between the Hegu point and the orofacial part.
Observations on the biology of Nile tilapia, Oreochromis niloticus L., in two Ugandan crater lakes

In this study, we compare the diet, life history characters and abundance of Nile tilapia (Oreochromis niloticus) stocks between two crater lakes in western Uganda (Lake Nyamusingiri and Lake Kyasanduka) that differ in their history of fishing pressure. Both lakes support native fish communities, but also harbour populations of introduced O. niloticus. Lake Nyamusingiri was characterized by a higher relative and absolute abundance (CPUE) of haplochromine cichlids and a lower abundance of O. niloticus than in Lake Kyasanduka. In addition, the O. niloticus population in Lake Nyamusingiri exhibited a smaller mean size and a lower relative abundance of juveniles than in Lake Kyasanduka. These differences may reflect, at least in part, heavy exploitation of O. niloticus in this lake, as compared with Lake Kyasanduka where fishing was banned in 1988. In both lakes, the maximum size and size at maturity was small relative to other larger water bodies in the region. The Nile tilapia in both lakes were primarily herbivorous; with phytoplankton dominating the diet. In general, the condition of O. niloticus in the crater lakes was low relative to other larger lakes in the region. The low catch per unit effort of O. niloticus in Lake Nyamusingiri (7.8%) relative to Lake Kyasanduka (54.9%) suggests that overexploitation of the fishery is occurring, calling for careful monitoring and management of the system.
Flow cytometric analysis of Notch1 and Jagged1 expression in normal blood cells and leukemia cells

Notch1 and its ligand Jagged1 are proteins with important roles in the growth of leukemia cells. Although the detection of Notch1 protein in acute lymphoblastic leukemia cells using immunoblot analysis has been previously reported, the expression patterns of Notch1 and Jagged1 detected by flow cytometry (FCM) in normal blood cells and various leukemia cells have not been well-characterised. In the present study, we examined the expression patterns of Notch1 and Jagged1 in 10 normal blood samples, 8 bone marrow samples, 11 leukemia/lymphoma cell lines and leukemia cells from 22 patients with acute myeloid leukemia (AML), mature T-cell neoplasms or B-cell chronic lymphocytic leukemia (B-CLL) using FCM. The results showed that Notch1 expression is relatively strong in monocytes and granulocytes but weak in lymphocytes. The expression of Notch1 is stronger in bone marrow cells than in the equivalent cells in blood. All the cell lines examined strongly expressed Notch1, and eight cell lines expressed Jagged1. In leukemia cells from patients, four AML samples expressed Notch1 and/or Jagged1. However, three samples expressed neither Notch1 and/or Jagged1 and none of the mature T-cell neoplasm samples expressed either protein. However, all B-CLL samples expressed high levels of both Notch1 and Jagged1. We found that the expression of Notch1 and Jagged1 is detected in various hematological malignancies by FCM. The examination of these proteins is likely to be useful in the characterisation of diseases and individual cases. Examination of these proteins may also be useful in the selection of patients most likely to benefit from novel molecular-targeted therapies using Notch inhibitors in the future.
Testing grain surface chemistry : a survey of deuterated formaldehyde and methanol in low-mass Class 0 protostars

Context. Despite the low cosmic abundance of deuterium (D/H ∼ 10 −5 ), high degrees of deuterium fractionation in molecules are observed in star-forming regions with enhancements that can reach 13 orders of magnitude, a level that current models have difficulty accounting for. Aims. Multi-isotopologue observations are a very powerful constraint for chemical models. The aim of our observations is to understand the processes that form the observed high abundances of methanol and formaldehyde in low-mass protostellar envelopes (gas-phase processes? chemistry on the grain surfaces? ), as well as to better constrain the chemical models. Methods. With the IRAM 30 m single-dish telescope, we observed deuterated formaldehyde (HDCO and D2CO) and methanol (CH2DOH, CH3OD, and CHD2OH) towards a sample of seven low-mass class 0 protostars. Using population diagrams, we then derived the fractionation ratios of these species (abundance ratio between the deuterated molecule and its main isotopologue) and compared them to the predictions of grain chemistry models. Results. These protostars show a similar level of deuteration as in IRAS 16293−2422, where doubly-deuterated methanol – and even triply-deuterated methanol – were first detected. Our observations point to the formation of methanol on the grain surfaces, while formaldehyde formation cannot be fully pinned down. While none of the scenarii can be excluded (gas-phase or grain chemistry formation), they both seem to require abstraction reactions to reproduce the observed fractionations.
OptiTuner: An Automatic Distributed Performance Optimization Service and a Server Farm Application

The next generation of real-time performance-sensitive systems is expected to be more distributed and dynamic. They will have multiple “knobs" that affect performance and resource allocation. Settings of these knobs will need to be jointly and dynamically optimized in the face of a changing workload and resource supply. Centralized approaches, such as Q-RAM, can efficiently maximize global utility of systems of multiple resources and constraints. As such systems grow in scale, complexity, and distribution, distributed solutions may be preferred at run-time. This paper uses optimization decomposition, recently applied at length in network theory, to break complex system-wide global optimization problems into less coupled subproblems that can be optimally solved at run-time in a distributed fashion. We develop a software service, called OptiTuner, that monitors the current performance and the resource availability in a performance-sensitive system and executes the distributed global optimization algorithm derived from optimization decomposition to maximize utility subject to resource and performance constraints. We apply OptiTuner to perform distributed energy optimization in a real-time Web server farm. We show that our distributed solutions achieve roughly up to 14% lower energy consumption than previous literature in our server farm testbed comprising of 18 machines.
Grapheme-color and tone-color synesthesia is associated with structural brain changes in visual regions implicated in color, form, and motion

Synesthesia is a rare condition in which stimulation in one modality leads to a secondary experience in another sensory modality. Varying accounts attribute the condition to either neuroanatomical differences between the synesthetes and non-synesthetes or functional differences in how sensory brain regions interact. This study employed voxel-based morphometry to examine whether synesthetes who experience both grapheme-color and tone-color synesthesia as their evoked sensation show neuroanatomical differences in gray matter volume compared to non-synesthetes. We observed that synesthetes showed an increase in gray matter volume in left posterior fusiform gyrus (FG), but a concomitant decrease in anterior regions of left FG and left MT/V5. These findings imply that synesthesia for color is linked to neuroanatomical changes between adjacent regions of the visual system.
An Extension Of The Acid Rain Theorem

Program fusion (or deforestation) is a well-known transformation whereby compositions of several pieces of code are fused into a single one, resulting in an ecient functional program without intermediate data structures. Recent work has made it clear that fusion transformation is especially successful if recursions are expressed in terms of hylomorphisms. The point of this success is that fusion transformation proceeds merely based on a simple but eective rule called Acid Rain Theorem [10]. However, there remains a problem. The Acid Rain Theorem can only handle hylomorphisms inducting over a single data structure. For hylomorphisms, like zip, which induct over multiple data structures, it will leave some of the data structures remained which should be removed. In this paper, we extend the Acid Rain Theorem so that it can deal with such hylomorphisms, enabling more intermediate data structures to be eliminated.
Reconstructing extracellular local field potential in cerebellar granular layer networks

Local field potentials (LFPs) arise from complex interactions of spatial distribution of current sources, time dynamics, spatial distribution of dipoles apart underlying conductive properties of the extracellular medium. We reconstruct LFP in order to test and parameterize the molecular mechanisms of cellular function with network properties. The sensitivity of LFP to local excitatory and inhibitory connections was tested using two novel approaches. In the first, we used a single granule neuron as a model kernel for reconstructing population activity. The second approach consisted using a detailed network model. L TP and LTD could regulate the spatiotemporal pattern of granular layer responses to mossy fiber inputs. The effect of changes in synaptic release probability and modulation in intrinsic excitability of granule cell on LFP was studied. The study revealed cellular function was represented in LFP wave revealing the activity of underlying neurons. Changes to cell during L TP and LTD were reflected by LFP wave as an indicator of the function of granule neurons as spatial pattern generators. Both modeling approaches generated LFP in vitro [16] and in vivo [17] waveforms as reported in experiments.
Guanxi Orientation and Subjective Norms in Knowledge Sharing: the Mediating effects of Loss of Knowledge Power and Codify Effort

Although knowledge sharing has been widely treated as the important factor for the success of an organization, relatively little work on exploring how to promote employees’ knowledge sharing has been done in the Chinese context. Due to the unique cultural background, attitudes, and values of the Chinese people, it is likely that the lessons gained from knowledge management practices in developed countries will not apply directly in the Chinese context. In this study, we draw upon the social capital theory to explore how two Chinese social capital, guanxi orientation and subjective norms, affect knowledge sharing. Specifically, our study proposes that loss of knowledge power and codify effort have a mediating effect on the relationship between social capital and knowledge sharing intention. A survey conducted in China was employed to test the hypotheses. The results indicate that guanxi orientation increases knowledge sharing intention through reducing loss of knowledge power. While subjective norms increase knowledge sharing intention through promoting codify effort. Theoretical and practical implications, as well as directions for future research are discussed.
Impact of trade factors on economic growth: seemingly unrelated regression model

This study explores the impact of trade on the economic growth, using seemingly unrelated regression model for SAARC countries namely Bangladesh, India, Pakistan and Srilanka for the period of 1980-2012. Trade factors include total exports, total imports, terms of trade, trade openness and investment. The results indicate the strong correlation between trade factors and economic growth, however, the magnitude of influencing economic growth varies factors to factors of international trade.
The Governance of the New Enterprise

The changing nature of the corporation forces us to re-examine much of what we take for granted in corporate governance. What precisely is the entity that is being governed? How does the governance system obtain power over it, and what determines the division of power between various stakeholders? And is the objective of allocating power only to enhance the returns of outside investors? In this paper we argue that, given the changing nature of the firm, the focus of corporate governance must shift from alleviating the agency problems between managers and shareholders to studying mechanisms that give the firm the power to provide incentives to human capital. We also provide some examples of the kind of subjects that should now be the main focus of study in corporate governance.
Multiyear search for dark matter annihilations in the Sun with the AMANDA-II and IceCube detectors

A search for an excess of muon neutrinos from dark matter annihilations in the Sun has been performed with the AMANDA-II neutrino telescope using data collected in 812 days of live time between 2001 and 2006 and 149 days of live time collected with the AMANDA-II and the 40-string configuration of IceCube during 2008 and early 2009. No excess over the expected atmospheric neutrino background has been observed. We combine these results with the previously published IceCube limits obtained with data taken during 2007 to obtain a total live time of 1065 days. We provide an upper limit at 90% confidence level on the annihilation rate of captured neutralinos in the Sun, as well as the corresponding muon flux limit at the Earth, both as functions of the neutralino mass in the range 50-5000 GeV. We also derive a limit on the neutralino-proton spin-dependent and spin-independent cross section. The limits presented here improve the previous results obtained by the collaboration between a factor of 2 and 5, as well as extending the neutralino masses probed down to 50 GeV. The spin-dependent cross section limits are the most stringent so far for neutralino masses above 200 GeV, and well below direct search results in the mass range from 50 GeV to 5 TeV.
Stage-Regulated GFP Expression in Trypanosoma cruzi: Applications from Host-Parasite Interactions to Drug Screening

Trypanosoma cruzi is the etiological agent of Chagas disease, an illness that affects about 10 million people, mostly in South America, for which there is no effective treatment or vaccine. In this context, transgenic parasites expressing reporter genes are interesting tools for investigating parasite biology and host-parasite interactions, with a view to developing new strategies for disease prevention and treatment. We describe here the construction of a stably transfected fluorescent T. cruzi clone in which the GFP gene is integrated into the chromosome carrying the ribosomal cistron in T. cruzi Dm28c. This fluorescent T. cruzi produces detectable amounts of GFP only at replicative stages (epimastigote and amastigote), consistent with the larger amounts of GFP mRNA detected in these forms than in the non replicative trypomastigote stages. The fluorescence signal was also strongly correlated with the total number of parasites in T. cruzi cultures, providing a simple and rapid means of determining the growth inhibitory dose of anti-T.cruzi drugs in epimastigotes, by fluorometric microplate screening, and in amastigotes, by the flow cytometric quantification of T. cruzi-infected Vero cells. This fluorescent T. cruzi clone is, thus, an interesting tool for unbiased detection of the proliferating stages of the parasite, with multiple applications in the genetic analysis of T. cruzi, including analyses of host-parasite interactions, gene expression regulation and drug development.
Initial results from the use of learning classifier systems to control in vitro neuronal networks

In this paper we describe the use of a learning classifier system to control the electrical stimulation of cultured neuronal networks. The aim is to manipulate the environment of the cells such that they display elementary learning, i.e., so that they respond to a given input signal in a pre-specified way. Results indicate that this is possible and that the learned stimulation protocols identify seemingly fundamental properties of in vitro neuronal networks.allUse of another learning scheme and simpler stimulation confirms these properties.
An investigation of Hybrid Simulation for modeling sustainability in healthcare

There is increasing awareness among stakeholders in healthcare that the present day reforms in this sector need to be structured around financial, environmental and social sustainability. This arguably serves as a motivation to investigate ways to incorporate sustainable development measures into their planning cycles, and furthermore to implement these plans through delivery of sustainable services. Use of Modeling & Simulation (M&S) is essential for such planning as it provides the stakeholders with a tool to experiment with alternative strategies and to evaluate the resultant simulation output in terms of both productivity-related criteria and sustainability-related metrics. This paper presents a hybrid M&S approach for sustainability analysis that relies on both “Discrete” and “Continuous” elements for the purpose of modeling strategic and operational aspects of the underlying healthcare system. An existing case study is discussed through the lens of the proposed new Hybrid Simulation Framework for TBL Modeling (HSF-TBL).
Adaptive Gating for Multitarget Tracking With Gaussian Mixture Filters

In this correspondence, we use a generalization of the Bayesian approach to the multitarget problem that goes under the name of cardinalized probability hypothesis density (CPHD) filter to jointly estimate a time varying number of targets and their locations from sets of noisy range measurements. While in the case of Gaussian linear models a closed-form solution for the CPHD recursion exists in the form of a Gaussian mixture (GM), the more general case of nonlinear systems suboptimal solutions becomes necessary. Due to the Gaussianity assumption in the the GM-CPHD filter, we propose to integrate the square-root cubature Kalman filter (S-CKF) into the GM-CPHD recursion. A novel weighted gating strategy, which exploits the GM implementation of the proposed S-CKF-GM-CPHD filter, is offered to lower the computational time by adaptively increasing the gate sizes in proportion to the likelihood of the single GM components. The results reveal that the proposed gating yields considerable savings in processing requirements compared to no gating, without any significant degradation in performance. In addition, although the run time improvement achieved with elliptical or adaptive gating is equivalent, the latter does not degrade the results.
An Empirical Study of Clone Removals

It is often claimed that duplicated source code is a threat to the maintainability of a software system and that developers should manage code duplication. A previous study analyzed the evolution of four software systems and found a remarkable discrepancy between code clones detected by a state-of-the-art clone detector and those deliberately removed by developers as the scope of the clones hardly ever matched. However, the results are based on a relatively small amount of data and need to be validated by a more extensive analysis. In this paper, we present an extension of this study by analyzing deliberate as well as accidental removals of code duplication in the evolution of eleven systems. Based on our findings, we could confirm the results of the previous study. Beyond that we found that accidental removals of cloned code occur slightly more often than deliberate removals and that many clone removals were in fact incomplete.
Squeezed everywhere - disentangling types of liquidity and testing limits-to-arbitrage

This doctoral thesis consists of 4 self-contained chapters:Sovereign Credit Default Swap Premia. This comprehensive review of the literature on sovereign CDS spreads highlights current academic debates and contrasts them with contradictory statements from the popular press. Real Economic Shocks and Sovereign Credit Risk. New empirical evidence highlights that global macroeconomic risk unspanned by global financial risk bears some responsibility for the strong co-movement in sovereign spreads. A model with only two global macroeconomic state variables rationalizes the existence of time-varying risk premia as a compensation for exposure to common U.S. business cycle risk.The Term Structure of CDS Spreads and Sovereign Credit Risk. The term structure of CDS spreads is an informative signal about the relative importance of global and country-specific risk factors for the time variation of sovereign credit spreads. An empirically validated model illustrates how local risk matters relatively more when the slope is negative, while systematic risk bears more responsibility when the slope is positive.Squeezed Everywhere - Disentangling Types of Liquidity and Testing Limits-to-Arbitrage. The CDS-Bond basis is used as a laboratory to disentangle different types of liquidity and to test limits-of-arbitrage. While asset-specific liquidity is cross-correlated in both the cash and derivative market, funding and market liquidity matter only for the former. The tests find strong evidence in favor of margin-based asset pricing and flight-to-quality effects.