Miracle-dz/UniFAR-FTUs huggingface dataset:
Assessing the relevance of ecotoxicological studies for regulatory decision making

Regulatory policies in many parts of the world recognize either the utility of or the mandate that all available studies be considered in environmental or ecological hazard and risk assessment (ERA) of chemicals, including studies from the peer‐reviewed literature. Consequently, a vast array of different studies and data types need to be considered. The first steps in the evaluation process involve determining whether the study is relevant to the ERA and sufficiently reliable. Relevance evaluation is typically performed using existing guidance but involves application of “expert judgment” by risk assessors. In the present paper, we review published guidance for relevance evaluation and, on the basis of the practical experience within the group of authors, we identify additional aspects and further develop already proposed aspects that should be considered when conducting a relevance assessment for ecotoxicological studies. From a regulatory point of view, the overarching key aspect of relevance concerns the ability to directly or indirectly use the study in ERA with the purpose of addressing specific protection goals and ultimately regulatory decision making. Because ERA schemes are based on the appropriate linking of exposure and effect estimates, important features of ecotoxicological studies relate to exposure relevance and biological relevance. Exposure relevance addresses the representativeness of the test substance, environmental exposure media, and exposure regime. Biological relevance deals with the environmental significance of the test organism and the endpoints selected, the ecological realism of the test conditions simulated in the study, as well as a mechanistic link of treatment‐related effects for endpoints to the protection goal identified in the ERA. In addition, uncertainties associated with relevance should be considered in the assessment. A systematic and transparent assessment of relevance is needed for regulatory decision making. The relevance aspects also need to be considered by scientists when designing, performing, and reporting ecotoxicological studies to facilitate their use in ERA. Integr Environ Assess Manag 2017;13:652–663. © 2016 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC)
Thomsen-Friedenreich and Tn Antigens in Nipple Fluid: Carbohydrate Biomarkers for Breast Cancer Detection

Purpose: Novel biomarkers would facilitate early and accurate diagnosis of breast cancer. The Thomsen-Freidenreich (TF) and Tn antigens are aberrantly glycosylated carbohydrate cancer-associated antigens found in ∼80% of adenocarcinomas. Both TF and Tn are expressed on cell-surface glycoproteins and glycolipids. Nipple aspirate fluid (NAF) is concentrated in secreted proteins and lipids from cells that give rise to cancer. The objective of this study was to determine if NAF from breasts with cancer contains elevated levels of TF and Tn compared with NAF from normal breasts. A sensitive and specific antigen capture immunoassay for TF and Tn detection in NAF was developed for this purpose. Experimental Design: Fifty NAF samples, 25 from breasts with cancer and 25 from normal breasts, were examined. Antigen capture immunoassays were done on the samples using monoclonal antibodies that specifically recognized either TF or Tn antigen in NAF. These antibodies captured serially diluted NAF samples, and the concentration of TF or Tn was determined by comparing absorbance values against a standard curve generated from standard sources of TF or Tn. Results: TF and Tn were detected in 19 of 25 and 20 of 25 NAF samples from breasts with cancer, respectively, compared with 0 of 25 and 1 of 25 NAF samples from breasts without cancer (P < 0.001 for both TF and Tn). In 92% of the cancerous breast NAF samples tested, either TF or Tn was found. Conclusions: Simultaneous measurement of TF and Tn in NAF may facilitate the noninvasive detection of breast cancer and warrants further study.
Overview of Treatment in Infantile Spasms

Infantile Spasms is a rare disorder consisting of epileptic spasms that occur before the age of one year. This severe epilepsy affects about 0.31 in 1000 births with an average age at onset of 6 months. Treatment usually consists of hormonal therapies (adrenocorticotropic hormone or corticosteroids) or vigabatrin. Decisions about choice of therapy are complicated because these first-line treatments can have significant side effects, are often expensive, and there are few randomized, controlled, blinded studies to guide therapy. Hormonal therapies are the most common first-line treatments and multiple trials suggest that they are the most effective. Vigabatrin may be more effective in treating infantile spasms in patients with tuberous sclerosis. Studies evaluating long-term cognitive outcomes in patients with infantile spasms have failed to show that any therapy produces superior long-term cognitive outcomes in all types of patients. However, there are some data suggesting that early treatment with hormonal therapies improves outcomes in patients for whom a cause of infantile spasms is never found. In this article, we review the evidence for available treatments for infantile spasms.
Chemokine Co-Receptor CCR5/CXCR4-Dependent Modulation of Kv2.1 Channel Confers Acute Neuroprotection to HIV-1 Glycoprotein gp120 Exposure

Infection with human immunodeficiency virus-1 (HIV-1) within the brain has long been known to be associated with neurodegeneration and neurocognitive disorder (referred as HAND), a condition characterized in its early stages by declining cognitive function and behavioral disturbances. Mechanistically, the HIV-1 coat glycoprotein 120 (gp120) has been suggested to be a critical factor inducing apoptotic cell death in neurons via the activation of p38 mitogen-activated protein kinase (MAPK), upon chronic exposure to the virus. Here we show that acute exposure of neurons to HIV-1 gp120 elicits a homeostatic response, which provides protection against non-apoptotic cell death, involving the major somatodendritic voltage-gated K+ (Kv) channel Kv2.1 as the key mediator. The Kv2.1 channel has recently been shown to provide homeostatic control of neuronal excitability under conditions of seizures, ischemia and neuromodulation/neuroinflammation. Following acute exposure to gp120, cultured rat hippocampal neurons show rapid dephosphorylation of the Kv2.1 protein, which ultimately leads to changes in specific sub-cellular localization and voltage-dependent channel activation properties of Kv2.1. Such modifications in Kv2.1 are dependent on the activation of the chemokine co-receptors CCR5 and CXCR4, and subsequent activation of the protein phosphatase calcineurin. This leads to the overall suppression of neuronal excitability and provides neurons with a homeostatic protective mechanism. Specific blockade of calcineurin and Kv2.1 channel activity led to significant enhancement of non-apoptotic neuronal death upon acute gp120 treatment. These observations shed new light on the intrinsic homeostatic mechanisms of neuronal resilience during the acute stages of neuro-HIV infections.
Amlodipine in hypertension: a first-line agent with efficacy for improving blood pressure and patient outcomes

Objectives Hypertension is well established as a major risk factor for cardiovascular disease. Although there is undeniable evidence to support the beneficial effects of antihypertensive therapy on morbidity and mortality, adequate blood pressure management still remains suboptimal. Research into the treatment of hypertension has produced a multitude of drug classes with different efficacy profiles. These agents include β-blockers, diuretics, ACE inhibitors, angiotensin receptor blockers and calcium channel blockers. One of the oldest groups of antihypertensives, the calcium channel blockers are a heterogeneous group of medications. Methods This review paper will focus on amlodipine, a dihydropyridine calcium channel blockers, which has been widely used for 2 decades. Results Amlodipine has good efficacy and safety, in addition to strong evidence from large randomised controlled trials for cardiovascular event reduction. Conclusions Amlodipine should be considered a first-line antihypertensive agent.
Spectral Properties of the Alignment Matrices in Manifold Learning

Local methods for manifold learning generate a collection of local parameterizations which is then aligned to produce a global parameterization of the underlying manifold. The alignment procedure is carried out through the computation of a partial eigendecomposition of a so-called alignment matrix. In this paper, we present an analysis of the eigenstructure of the alignment matrix giving both necessary and sufficient conditions under which the null space of the alignment matrix recovers the global parameterization. We show that the gap in the spectrum of the alignment matrix is proportional to the square of the size (the precise definition of the size is given in section sec:sp) of the overlap of the local parameterizations, thus deriving a quantitative measure of how stably the null space can be computed numerically. We also give a perturbation analysis of the null space of the alignment matrix when the computation of the local parameterizations is subject to error. Our analysis provides insights into the behaviors and performance of local manifold learning algorithms.
A design model of emotional body expressions in non-humanoid robots

Robotic emotional expressions could benefit social communication between humans and robots, if the cues such expressions contain were to be intelligible to human observers. In this paper, we present a design framework for modelling emotionally expressive robotic movements. The framework combines approach-avoidance with Shape and Effort dimensions, derived from Laban, and makes use of anatomical body planes that are general to both humanoid and non-humanoid body forms. An experimental validation study is reported with 34 participants rating an implementation of five expressive behaviours on a non-humanoid robotic platform. The results demonstrate that such expressions can encode basic emotional information, in that the parameters of the proposed design model can convey the meaning of emotional dimensions of valence, arousal and dominance. The framework thus creates a basis for implementing a set of emotional expressions that are appropriately adapted to contexts of human-robot joint activity.
Residues of E. coli topoisomerase I conserved for interaction with a specific cytosine base to facilitate DNA cleavage

Bacterial and archaeal topoisomerase I display selectivity for a cytosine base 4 nt upstream from the DNA cleavage site. Recently, the solved crystal structure of Escherichia coli topoisomerase I covalently linked to a single-stranded oligonucleotide revealed that R169 and R173 interact with the cytosine base at the −4 position via hydrogen bonds while the phenol ring of Y177 wedges between the bases at the −4 and the −5 position. Substituting R169 to alanine changed the selectivity of the enzyme for the base at the −4 position from a cytosine to an adenine. The R173A mutant displayed similar sequence selectivity as the wild-type enzyme, but weaker cleavage and relaxation activity. Mutation of Y177 to serine or alanine rendered the enzyme inactive. Although mutation of each of these residues led to different outcomes, R169, R173 and Y177 work together to interact with a cytosine base at the −4 position to facilitate DNA cleavage. These strictly conserved residues might act after initial substrate binding as a Molecular Ruler to form a protein–DNA complex with the scissile phosphate positioned at the active site for optimal DNA cleavage by the tyrosine hydroxyl nucleophile to facilitate DNA cleavage in the reaction pathway.
A Dearth of Dark Matter in Ordinary Elliptical Galaxies

The kinematics of the outer parts of three intermediate-luminosity elliptical galaxies were studied with the Planetary Nebula Spectrograph. The galaxies' velocity-dispersion profiles were found to decline with the radius, and dynamical modeling of the data indicates the presence of little if any dark matter in these galaxies' halos. This unexpected result conflicts with findings in other galaxy types and poses a challenge to current galaxy formation theories.
Salzmann Nodular Degeneration

Purpose: To describe the characteristic, clinical, and epidemiological features of Salzmann nodular degeneration. Methods: Retrospective review of cases. All patients with diagnosis of Salzmann nodular degeneration examined on the Cornea and External Disease Service in the Department of Ophthalmology and Vision Science at the University of California, Davis, were included in this review. Demographic features, clinical characteristics, treatment regimens, surgical procedures, and outcomes were recorded. Descriptive statistics, correlation statistics in bilateral cases, and simple regression models were constructed to assess the effect of potential indicators of severity. Results: One hundred eighty eyes of 108 patients were included in this review. Seventy-nine patients (72.2%) were female and 29 (27.8%) were male. Seventy-two patients had bilateral disease. The mean age for all patients was 60.8 (13-92) years, and the mean follow-up time was 61.2 months (0-357 months). 76.1% of all eyes were from White. Mean logarithm of the minimum angle of resolution best-corrected visual acuity was 0.24 (Snellen equivalent 20/35, range −0.12 to 2.60, SD 0.44). Decreased visual acuity was the most common symptom in 30.6% of patients. The visual axis was affected in 30% of the cases. Meibomian gland dysfunction was the most common coexistent condition, identified in 41.7% of the cases. For bilateral cases, Spearman correlations for best-corrected visual acuity, magnitude of astigmatism, spherical equivalent, and disease extension were statistically significant (P = 0.001). The number of quadrants affected was found to be a significant predictor for astigmatism (P = 0.01). Surgery was indicated in 41 eyes of 30 patients. Decreased visual acuity was the most common indication for superficial keratectomy. Patients with more than 1 quadrant of the cornea affected or those in which the central visual axis was involved were more likely to require surgery (P = 0.015 and 0.0001, respectively). The surgical outcome was satisfactory in 90.2% of the cases; 9 eyes (21.9%) developed recurrences. Conclusions: Salzmann nodular degeneration is a disease of uncertain etiology in which inflammation of the ocular surface may play a role. It predominantly affects women in the sixth decade of life. Management with conservative therapy is generally adequate, and in cases that require surgical intervention, simple nodulectomy is usually effective.
Attribute-based clustering for information dissemination in wireless sensor networks

Data routing in large wireless sensor networks is challenged by requirements for scalability, robustness, and energy use, as well as the possibility that globally unique identifiers for each node are nonexistent. Moreover, if the sensor network serves multiple functions or users, its routing function must be energy efficient when responding to information requests (inquiries) that can arrive at high rates, require diverse data types, and target subsets of the sensor network. We propose virtual "containment" hierarchies based on relevant attributes as a more efficient mechanism to disseminate inquiries rather than theuse of flooding schemes. We show algorithms that support clustering sensors according to these hierarchies and implement clusterhead failure recovery and load balancing among cluster members. We show that our framework has significant bandwidth gains over a flooding-based scheme under the scenario considered using analytical techniques.
Effect of nutrient management on growth and yield of niger (Guizotia abyssinica L.)

The field investigation entitled “Effect of nutrient management on growth and yield of niger (Guizotia abyssinica L.)” was conducted at experimental research farm, Department of Agronomy, Vasantrao Naik Marathwada Krishi Vidyapeeth, Parbhani. The experimental field was leveled and well drained. The soil was clayey in texture, low in nitrogen, medium in phosphorus and high in potassium with alkaline in reaction. The environmental conditions prevailed during experimental period was favorable for normal growth and maturity of niger crop.The experiment was laid out in a randomized block design with five treatments and four replications. The treatments were 100 % RDF (T1) , 100 % RDF + one foliar application of 2 % urea at flowering (T2) , 100 % RDF + Two foliar application of 2 % urea at flowering + capitula formation (T3), 75 % RDF + one foliar application of 2 % urea at flowering (T4), 75 % RDF + Two foliar application of 2 % urea at flowering + capitula formation (T5). Sowing was done on 28 June, 2016 by dibbling the seeds at spacing 30 cm x 10 cm. The recommended cultural practices and plant protection measures were taken. The recommended dose of fertilizer (20:40:00 NPK kg ha) was applied at the time of sowing through Urea and DAP. The crop was harvested on 29 September, 2016. Application of 100 % RDF + Two foliar application of 2 % urea (T3) to niger crop recorded significantly higher values in growth attributes and seed yield (549 kg ha) as well as straw yield (4359 kg ha) followed by the treatment T2 i.e. 100 % RDF + one foliar application of 2 % urea at flowering. In case of monetary returns, the treatment T3 recorded significantly higher gross monetary returns (GMR) 22227 ha, net monetary returns (NMR) 9194 ha and B:C ratio 1.71 with same trend followed by the treatment T2. On the basis of above findings it may be inferred that, for getting maximum seed yield, net returns and B:C ratio, application of 100 % RDF with two foliar application of 2 % urea at flowering and capitula formation (T3) was found to be effective in increasing production of niger crop.
When Like Charges Attract: The Effects of Geometrical Confinement on Long-Range Colloidal Interactions.

High-resolution measurements of the interaction potential between pairs of charged colloidal microspheres suspended in water provide stringent tests for theories of colloidal interactions. The screened Coulomb repulsions we observe for isolated spheres agree quantitatively with predictions of the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory. Confining the same spheres between charged glass walls, however, induces a strong long-range attractive interaction which is not accounted for by the DLVO theory. [S0031-9007(96)01030-7]
c-Kit-dependent growth of uveal melanoma cells: a potential therapeutic target?

PURPOSE This study was conducted to investigate the expression and functional impact of the proto-oncogene c-kit in uveal melanoma. METHODS Based on immunohistochemical (IHC) study of paraffin-embedded specimens from 134 uveal melanomas and Western blot analysis on eight fresh-frozen samples the expression of c-kit in uveal melanoma was studied. Furthermore, the phosphorylation of c-kit and the impact of the tyrosine kinase inhibitor STI571 was examined in the three uveal melanoma cell lines OCM-1, OCM-3, and 92-1. RESULTS Eighty-four of 134 paraffin-embedded samples and six of eight fresh-frozen samples expressed c-kit. c-Kit was strongly expressed and tyrosine phosphorylated in cultured uveal melanoma cells compared with cutaneous melanoma cells. Moreover, in contrast to cutaneous melanoma cell lines c-kit maintained a high phosphorylation level in serum-depleted uveal melanoma cells. No activation-related mutations in exon 11 of the KIT gene were found. On the contrary, expression of the stem cell growth factor (c-kit ligand) was detected in all three uveal melanoma cell lines, suggesting the presence of autocrine (paracrine) stimulation pathways. Treatment of uveal melanoma cell lines with STI571, which blocks c-kit autophosphorylation, resulted in cell death. The IC(50) of the inhibitory effects on c-kit phosphorylation and cell proliferation was of equal size and less than 2.5 microM. CONCLUSIONS The results confirm that c-kit is vastly expressed in uveal melanoma, suggest that the c-kit molecular pathway may be important in uveal melanoma growth, and point to its use as a target for therapy with STI571.
The neural correlates of risk propensity in males and females using resting-state fMRI

Men are more risk prone than women, but the underlying basis remains unclear. To investigate this question, we developed a trait-like measure of risk propensity which we correlated with resting-state functional connectivity to identify sex differences. Specifically, we used short- and long-range functional connectivity densities to identify associated brain regions and examined their functional connectivities in resting-state functional magnetic resonance imaging (fMRI) data collected from a large sample of healthy young volunteers. We found that men had a higher level of general risk propensity (GRP) than women. At the neural level, although they shared a common neural correlate of GRP in a network centered at the right inferior frontal gyrus, men and women differed in a network centered at the right secondary somatosensory cortex, which included the bilateral dorsal anterior/middle insular cortices and the dorsal anterior cingulate cortex. In addition, men and women differed in a local network centered at the left inferior orbitofrontal cortex. Most of the regions identified by this resting-state fMRI study have been previously implicated in risk processing when people make risky decisions. This study provides a new perspective on the brain-behavioral relationships in risky decision making and contributes to our understanding of sex differences in risk propensity.