Miracle-dz/UniFAR-FTUs huggingface dataset:
Can the choice of endpoint lead to contradictory results of mixture‐toxicity experiments?

Theoretically, the effect of two independently acting compounds in a mixture will depend on the slope of the dose‐response curves of the individual compounds if evaluated in relation to the model of concentration addition (CA). In the present study, we explored development of the shape of the dose‐response relationship for four different recommended endpoints (surface area, frond number, fresh weight‐specific, and dry weight‐specific relative growth rates [RGRA, RGRF, RGRFW, and RGRDW, respectively]) and for two differently acting herbicides (metsulfuron‐methyl and terbuthylazine) over time (3–15 d) on the standard test plant Lemna minor to identify endpoints and experiment times for which predictions of independent action (IA) would depart the most from those of CA. After a test time of 6 d, predictions of IA based on RGRA and RGRFW showed antagonism in relation to CA. Based on RGRDW, synergy was predicted, whereas IA based on RGRF was indistinguishable from CA. To test the prediction of choice of endpoint giving different results in mixture‐toxicity experiments, three endpoints and six combinations of independently acting herbicides were evaluated using isobolograms. The experiments showed that in four of six herbicide combinations, different conclusions were reached depending on endpoint. The contradictory isoboles did not follow the theory of IA and, therefore, are more likely to be related to differences in susceptibility of the physiological processes affecting each endpoint than to the shape of the dose‐response curve.
PlasmoGEM, a database supporting a community resource for large-scale experimental genetics in malaria parasites

The Plasmodium Genetic Modification (PlasmoGEM) database (http://plasmogem.sanger.ac.uk) provides access to a resource of modular, versatile and adaptable vectors for genome modification of Plasmodium spp. parasites. PlasmoGEM currently consists of >2000 plasmids designed to modify the genome of Plasmodium berghei, a malaria parasite of rodents, which can be requested by non-profit research organisations free of charge. PlasmoGEM vectors are designed with long homology arms for efficient genome integration and carry gene specific barcodes to identify individual mutants. They can be used for a wide array of applications, including protein localisation, gene interaction studies and high-throughput genetic screens. The vector production pipeline is supported by a custom software suite that automates both the vector design process and quality control by full-length sequencing of the finished vectors. The PlasmoGEM web interface allows users to search a database of finished knock-out and gene tagging vectors, view details of their designs, download vector sequence in different formats and view available quality control data as well as suggested genotyping strategies. We also make gDNA library clones and intermediate vectors available for researchers to produce vectors for themselves.
Global smoothness preservation and the variation-diminishing property

In the center of our paper are two counterexamples showing the independence of the concepts of global smoothness preservation and variation diminution for sequences of approximation operators. Under certain additional assumptions it is shown that the variation-diminishing property is the stronger one. It is also demonstrated, however, that there are positive linear operators giving an optimal pointwise degree of approximation, and which preserve global smoothness, monotonicity and convexity, but are not variationdiminishing.
Dynamic, Nonlinear Feedback Regulation of Slow Pacemaking by A-Type Potassium Current in Ventral Tegmental Area Neurons

We analyzed ionic currents that regulate pacemaking in dopaminergic neurons of the mouse ventral tegmental area by comparing voltage trajectories during spontaneous firing with ramp-evoked currents in voltage clamp. Most recordings were made in brain slice, with key experiments repeated using acutely dissociated neurons, which gave identical results. During spontaneous firing, net ionic current flowing between spikes was calculated from the time derivative of voltage multiplied by cell capacitance, signal-averaged over many firing cycles to enhance resolution. Net inward interspike current had a distinctive nonmonotonic shape, reaching a minimum (generally <1 pA) between −60 and −55 mV. Under voltage clamp, ramps over subthreshold voltages elicited a time- and voltage-dependent outward current that peaked near −55 mV. This current was undetectable with 5 mV/s ramps and increased steeply with depolarization rate over the range (10–50 mV/s) typical of natural pacemaking. Ramp-evoked subthreshold current was resistant to α-dendrotoxin, paxilline, apamin, and tetraethylammonium but sensitive to 4-aminopyridine and 0.5 mm Ba2+, consistent with A-type potassium current (IA). Same-cell comparison of currents elicited by various ramp speeds with natural spontaneous depolarization showed how the steep dependence of IA on depolarization rate results in small net inward currents during pacemaking. These results reveal a mechanism in which subthreshold IA is near zero at steady state, but is engaged at depolarization rates >10 mV/s to act as a powerful, supralinear feedback element. This feedback mechanism explains how net ionic current can be constrained to <1–2 pA but reliably inward, thus enabling slow, regular firing.
Usability and education of games through combined assessment methods

In this paper we use evaluation methods that are mainly used in software so as to assess the usability of a video game. More specifically we examine the strategy game "Civilization IV" as well as the tutorial of the game. The study is using during the process of the experiment original evaluation methods as well as combined and the final results are of great interest. It is worth mentioning that we have used a strategy game which is not merely educational and evaluated to what extend it may contribute to the learning process.
Gross National Happiness: Why Happiness Matters for America--and How We Can Get More of It

Who are the happiest Americans? Surveys show that religious people think they are happier than secularists, and secularists think they are happier than religious people. Liberals believe they are happier than conservatives, and conservatives disagree. In fact, almost every group thinks it is happier than everyone else. In this provocative new book, Arthur C. Brooks explodes the myths about happiness in America. As he did in the controversial Who Really Cares: The Surprising Truth About Compassionate Conservatism, Brooks examines vast amounts of evidence and empirical research to uncover the truth about who is happy in America, who is not, and-most important-why. He finds that there is a real "happiness gap" in America today, and it lies disconcertingly close to America's cultural and political fault lines. The great divide between the happy and the unhappy in America, Brooks shows, is largely due to differences in social and cultural values. The values that bring happiness are faith, charity, hard work, optimism, and individual liberty. Secularism, excessive reliance on the state to solve problems, and an addiction to security all promote unhappiness. What can be done to maximize America's happiness? Replete with the unconventional wisdom for which Brooks has come to be known, Gross National Happiness offers surprising and illuminating conclusions about how our government can best facilitate Americans in their pursuit of happiness.
Recognition and Degradation of Myelin Basic Protein Peptides by Serum Autoantibodies: Novel Biomarker for Multiple Sclerosis1

The pathologic role of autoantibodies in autoimmune disease is widely accepted. Recently, we reported that anti-myelin basic protein (MBP) serum Abs from multiple sclerosis (MS) patients exhibit proteolytic activity toward the autoantigen. The aim of this study is to determine MBP epitopes specific for the autoantibodies in MS and compare these data with those from other neuronal disorders (OND), leading to the generation of new diagnostic and prognostic criteria. We constructed a MBP-derived recombinant “epitope library” covering the entire molecule. We used ELISA and PAGE/surface-enhanced laser desorption/ionization mass spectroscopy assays to define the epitope binding/cleaving activities of autoantibodies isolated from the sera of 26 MS patients, 22 OND patients, and 11 healthy individuals. The levels of autoantibodies to MBP fragments 48–70 and 85–170 as well as to whole MBP and myelin oligodendrocyte glycoprotein molecules were significantly higher in the sera of MS patients than in those of healthy donors. In contrast, selective reactivity to the two MBP fragments 43–68 and 146–170 distinguished the OND and MS patients. Patients with MS (77% of progressive and 85% of relapsing-remitting) but only 9% of patients with OND and no healthy donors were positive for catalysis, showing pronounced epitope specificity to the encephalitogenic MBP peptide 81–103. This peptide retained its substrate properties when flanked with two fluorescent proteins, providing a novel fluorescent resonance energy transfer approach for MS studies. Thus, anti-MBP autoantibody-mediated, epitope-specific binding and cleavage may be regarded as a specific characteristic of MS compared with OND and healthy donors and may serve as an additional biomarker of disease progression.
Global typology of urban energy use and potentials for an urbanization mitigation wedge

Significance Many case studies of specific cities have investigated factors that contribute to urban energy use and greenhouse-gas emissions. The analysis in this study is based on data from 274 cities and three global datasets and provides a typology of urban attributes of energy use. The results highlight that appropriate policies addressing urban climate change mitigation differ with type of city. A global urbanization wedge, corresponding in particular to energy-efficient urbanization in Asia, might reduce urban energy use by more than 25%, compared with a business-as-usual scenario. The aggregate potential for urban mitigation of global climate change is insufficiently understood. Our analysis, using a dataset of 274 cities representing all city sizes and regions worldwide, demonstrates that economic activity, transport costs, geographic factors, and urban form explain 37% of urban direct energy use and 88% of urban transport energy use. If current trends in urban expansion continue, urban energy use will increase more than threefold, from 240 EJ in 2005 to 730 EJ in 2050. Our model shows that urban planning and transport policies can limit the future increase in urban energy use to 540 EJ in 2050 and contribute to mitigating climate change. However, effective policies for reducing urban greenhouse gas emissions differ with city type. The results show that, for affluent and mature cities, higher gasoline prices combined with compact urban form can result in savings in both residential and transport energy use. In contrast, for developing-country cities with emerging or nascent infrastructures, compact urban form, and transport planning can encourage higher population densities and subsequently avoid lock-in of high carbon emission patterns for travel. The results underscore a significant potential urbanization wedge for reducing energy use in rapidly urbanizing Asia, Africa, and the Middle East.
Calligraphic packing

There are many algorithms in non-photorealistic rendering for representing an image as a composition of small objects. In this paper, we focus on the specific case where the objects to be assembled into a composition are letters rather than images or abstract geometric forms. We develop a solution to the "calligraphic packing" problem based on dividing up a target region into pieces and warping a letter into each piece. We define an energy function that chooses a warp that best represents the original letter. We discuss variations in rendering style and show results produced by our system.
PLASMA CITRULLINE CONCENTRATION AS A MARKER OF SMALL INTESTINE FAILURE

Introduction Functional parameters for small bowel damage are not suited to routine examination in daily clinical practice. No blood markers have been identifi ed yet for a functional absorptive bowel length. Plasma citrulline, a non-protein amino acid produced by intestinal mucosa, is one possible candidate. Although produced in the liver, the small intestine is the main source for citrulline in the circulation. In healthy humans, plasma citrulline concentrations range from approximately 20 to 50 μmol/l. Our study in patients with short bowel syndrome (SBS) was carried out to investigate whether plasma amino acid levels and particularly citrulline concentrations could be a marker of functional absorptive bowel length.
Determination of total homocysteine in plasma: comparison of the Abbott IMx immunoassay with high performance liquid chromatography.

BACKGROUND AND OBJECTIVES The aim of this study was to compare the performance of a commercially available IMx immunoassay with that of a reversed-phase high performance liquid chromatography (HPLC) method for measuring plasma total homocysteine (tHcy). METHODS The levels of tHcy before and after oral methionine loading (ML) were measured in 135 healthy subjects and 39 patients scheduled for routine tHcy determination. The IMx method uses fluorescence polarization immunoassay (FPIA) technology. The HPLC-method includes derivatization with ABD-F and post-column fluorescence detection. RESULTS The imprecision was very low with both methods for both normal (11 mmol/L) and high (29 mmol/L) tHcy levels. The within and between-run coefficients of variation were < 5%. Both methods were able to discriminate between similar concentrations of tHcy both at normal and moderately high levels. There was a good correlation between measurements obtained with the two methods (r = 0.985, p = 0.001). The mean levels of tHcy measured with the IMx assay tended to be slightly higher than those with the HPLC both in the fasting state (mean difference = 0.8 mmol/L) and after ML (5.3 mmol/L). However only the difference in post-ML levels was statistically significant (p < 0.001). The percentage of patients with hyperhomocysteinemia identified with the two methods was similar. INTERPRETATION AND CONCLUSIONS The IMx method compares well with an established HPLC method for measurement of fasting tHcy plasma levels.
Evidence for an Enhanced Transmembrane Sodium (Na+) Gradient Induced by Aldosterone in the Incubated Rat Tail Artery

Aldosterone is known to stimulate Na+ transport as measured in terms of current-carrying capacity of epithelial sheets or of Na+ — K+ ATPase activity in cells. The possibility that this is reflected in an altered steady-state transmembrane Na+ distribution in vascular smooth muscle was here examined directly. Transmembrane Na+ and K+ gradients were first dissipated by orernlght incubation in K-free physiological salt solution (PSS) at 10°C and then reesUblished by 3 hours in normal PSS at 37°C. The addition of d-aldosterone (but not corticosterone) to these media significantly reduced cell Na. This involved only free cell Na which was reduced by about 20% or 3 mmole/kg dry wt. No significant change in membrane permeability measured in terms of net Li uptake at 3°C or at 37°C was observed. The lowest effective aldosterone concentration was 2.8 × 10−2 M. These results are consistent with the observed enhancement of net Na+ transport in incubated arteries in DOCA-induced hypertension and in the SHR but do not account for the increased Na+ permeability observed in these states. (Hypertension 4: 230–237, 1982)
Nursery school teachers' knowledge of emotional needs and use of appropriate guidance procedures

The purpose of this investigation was to ascertain the following: (l) nursery school teachers' knowledge of emotional needs of children and (2) nursery school teachers' use of appropriate guidance procedures. More specifically two major hypotheses were tested: (l) nursery school teachers' knowledge of emotional needs are unrelated to (a) number of years of teaching experience with threeand four-year-old children, (b) educational background of the teacher, (c) number of courses taken in college dealing with children, and (d) teacher scores on use of appropriate guidance procedures, and (2) teacher scores on use of appropriate guidance procedures are unrelated to: (a) years of experience working with threeand four-year-old children, (b) . educational background of teachers, (c) number of courses taken in college dealing with children, and (d) type <f school in which teachers are teaching. The subjects utilized in this study were fortyseven nursery school teachers in Tucson, Arizona, employed in nursery schools and day-care centers during the year 19 66-1967.
Improved parallel interference cancellation for CDMA

This paper introduces an improved nonlinear parallel interference cancellation scheme for code-division multiple access (CDMA) that significantly reduces the degrading effect on the desired user of interference from the other users that share the channel. The implementation complexity of the scheme is linear in the number of users and operates on the fact that parallel processing simultaneously removes from each user a part of the interference produced by the remaining users accessing the channel the amount being proportional to their reliability. The parallel processing can be done in multiple stages. The proposed scheme uses tentative decision devices at the multiple stages to produce the most reliably estimated received data for generation and cancellation of user interference. Simulation results are given for a multitude of different situations, in particular, those cases for which the analysis is too complex.
FUNCTION ALGEBRAS

Introduction. By a function algebra I shall mean a collection A of complex-valued functions on a set X such that the (pointwise) sum and the product of two functions in A are again in A. We shall always suppose that A contains the constant functions so that A becomes an algebra with unit over the field of complex numbers. A function algebra A is called self-ad joint if the complex conjugate of each function in A is again in A, and the theory of self-ad joint algebras is quite different from that of non-self-adjoint algebras. An example of a selfadjoint function algebra is given by the algebra of all continuous complex-valued functions on a topological space X. A thorough description of the theory of such algebras is given in the book by Gilman and Jerison [27]. My own interest in function algebras arose from the study of algebras of analytic functions on some sort of an analytic space X. These algebras are of course very far from being self-ad joint. A considerable amount of effort has gone into the study of certain of these algebras and of the relationship between algebraic properties of such an algebra and the analytic structure of the underlying space X. This includes work by Bers [8], Bishop, [lO; 12], Chevalley and Kakutani [43], Edwards [22], Heins [29], Helmer [30], Henriksen [33], Rudin [57], Wermer [70; 71 ] and myself [54; 55]. One of the principal purposes of the present discussion is to give a general treatment of function algebras into which many of the above results may be fitted. Another purpose is to illustrate the application of methods from the theory of functions of several complex variables to derive results about non-self-ad joint function algebras. Excellent examples of such applications are given in the papers by Arens and Calderon [2 ] and Rossi [52], and in §7 I use a theorem of Arens and mine to illustrate these techniques. This theorem describes the one-dimensional cohomology of the spectrum of a Banach algebra in terms of the group of invertible elements of the algebra. It generalizes to arbitrary commutative Banach algebras the theorems of Bruschlinsky [18] and Eilenberg [23], describing the one-dimensional cohomology of a compact set X in terms of C(X).
Virus-Cell Interactions Regulating Induction of Tumor Necrosis Factor Alpha Production in Macrophages Infected with Herpes Simplex Virus

ABSTRACT Macrophages respond to virus infections by rapidly secreting proinflammatory cytokines, which play an important role in the first line of defense. Tumor necrosis factor alpha (TNF-α) is one of the major macrophage-produced cytokines. In this study we have investigated the virus-cell interactions responsible for induction of TNF-α expression in herpes simplex virus (HSV)-infected macrophages. Both HSV type 1 (HSV-1) and HSV-2 induced TNF-α expression in macrophages activated with gamma interferon (IFN-γ). This induction was to some extent sensitive to UV treatment of the virus. Virus particles unable to enter the cells displayed reduced capacity to stimulate TNF-α expression but retained a significant portion which was abolished by HSV-specific antibodies. Recombinant HSV-1 glycoprotein D was able to trigger TNF-α secretion in concert with IFN-γ. Sugar moieties of HSV glycoproteins have been reported to be involved in induction of IFN-α but did not contribute to TNF-α expression in macrophages. Moreover, the entry-dependent portion of the TNF-α induction was investigated with HSV-1 mutants and found to be independent of the tegument proteins VP16 and UL13 and partly dependent on nuclear translocation of the viral DNA. Finally, we found that macrophages expressing an inactive mutant of the double-stranded RNA (dsRNA)-activated protein kinase (PKR) produced less TNF-α in response to infectious HSV infection than the empty-vector control cell line but displayed the same responsiveness to UV-inactivated virus. These results indicate that HSV induces TNF-α expression in macrophages through mechanisms involving (i) viral glycoproteins, (ii) early postentry events occurring prior to nuclear translocation of viral DNA, and (iii) viral dsRNA-PKR.
Modeling the Impact of Lesions in the Human Brain

Lesions of anatomical brain networks result in functional disturbances of brain systems and behavior which depend sensitively, often unpredictably, on the lesion site. The availability of whole-brain maps of structural connections within the human cerebrum and our increased understanding of the physiology and large-scale dynamics of cortical networks allow us to investigate the functional consequences of focal brain lesions in a computational model. We simulate the dynamic effects of lesions placed in different regions of the cerebral cortex by recording changes in the pattern of endogenous (“resting-state”) neural activity. We find that lesions produce specific patterns of altered functional connectivity among distant regions of cortex, often affecting both cortical hemispheres. The magnitude of these dynamic effects depends on the lesion location and is partly predicted by structural network properties of the lesion site. In the model, lesions along the cortical midline and in the vicinity of the temporo-parietal junction result in large and widely distributed changes in functional connectivity, while lesions of primary sensory or motor regions remain more localized. The model suggests that dynamic lesion effects can be predicted on the basis of specific network measures of structural brain networks and that these effects may be related to known behavioral and cognitive consequences of brain lesions.