Miracle-dz/UniFAR-FTUs huggingface dataset:
Quantifying immediate and delayed effects of anthelmintic exposure on ecosystem functioning supported by a common dung beetle species

Dung beetles (Coleoptera: Scarabaeoidea) support numerous ecosystem functions in livestock-grazed pastures. Exposure to veterinary anthelmintic residues in livestock dung can have lethal and sublethal effects on dung beetles, and can reduce rates of dung removal, but the immediate and longer-term consequences for other dung beetle mediated functions have rarely been studied. We investigated the consequences of anthelmintic exposure on survival of the dung beetle Aphodius fossor and its delivery of four ecosystems functions that underpin pasture production: dung removal, soil fauna feeding activity, primary productivity, and reduction of soil compaction. We tested whether anthelmintic exposure had immediate or delayed effects on these functions individually and simultaneously (i.e., ecosystem multifunctionality). We found no evidence that ivermectin residues had a lethal effect on adult beetles. For dung removal, we found a significant interaction between the timing of exposure and functioning: while dung removal was impaired by concurrent exposure to high levels of ivermectin, functioning was unaffected when beetles that had been exposed previously to the same concentration of anthelmintic later interacted with untreated dung. Other ecosystem functions were not affected significantly by anthelmintic exposure, and there was no evidence to suggest any persistent impact of anthelmintic exposure on ecosystem multifunctionality. While anthelmintic residues remain a significant threat to dung beetle populations, for adult beetles, we found no evidence that residues have detrimental consequences for ecosystem functioning beyond the immediate point of exposure.
Efficacy and tolerability of pegloticase for the treatment of chronic gout in patients refractory to conventional treatment: two randomized controlled trials.

CONTEXT Patients with chronic disabling gout refractory to conventional urate-lowering therapy need timely treatment to control disease manifestations related to tissue urate crystal deposition. Pegloticase, monomethoxypoly(ethylene glycol)-conjugated mammalian recombinant uricase, was developed to fulfill this need. OBJECTIVE To assess the efficacy and tolerability of pegloticase in managing refractory chronic gout. DESIGN, SETTING, AND PATIENTS Two replicate, randomized, double-blind, placebo-controlled trials (C0405 and C0406) were conducted between June 2006 and October 2007 at 56 rheumatology practices in the United States, Canada, and Mexico in patients with severe gout, allopurinol intolerance or refractoriness, and serum uric acid concentration of 8.0 mg/dL or greater. A total of 225 patients participated: 109 in trial C0405 and 116 in trial C0406. INTERVENTION Twelve biweekly intravenous infusions containing either pegloticase 8 mg at each infusion (biweekly treatment group), pegloticase alternating with placebo at successive infusions (monthly treatment group), or placebo (placebo group). MAIN OUTCOME MEASURE Primary end point was plasma uric acid levels of less than 6.0 mg/dL in months 3 and 6. RESULTS In trial C0405 the primary end point was reached in 20 of 43 patients in the biweekly group (47%; 95% CI, 31%-62%), 8 of 41 patients in the monthly group (20%; 95% CI, 9%-35%), and in 0 patients treated with placebo (0/20; 95% CI, 0%-17%; P < .001 and <.04 for comparisons between biweekly and monthly groups vs placebo, respectively). Among patients treated with pegloticase in trial C0406, 16 of 42 in the biweekly group (38%; 95% CI, 24%-54%) and 21 of 43 in the monthly group (49%; 95% CI, 33%-65%) achieved the primary end point; no placebo-treated patients reached the primary end point (0/23; 95% CI, 0%-15%; P = .001 and < .001, respectively). When data in the 2 trials were pooled, the primary end point was achieved in 36 of 85 patients in the biweekly group (42%; 95% CI, 32%-54%), 29 of 84 patients in the monthly group (35%; 95% CI, 24%-46%), and 0 of 43 patients in the placebo group (0%; 95% CI, 0%-8%; P < .001 for each comparison). Seven deaths (4 in patients receiving pegloticase and 3 in the placebo group) occurred between randomization and closure of the study database (February 15, 2008). CONCLUSION Among patients with chronic gout, elevated serum uric acid level, and allopurinol intolerance or refractoriness, the use of pegloticase 8 mg either every 2 weeks or every 4 weeks for 6 months resulted in lower uric acid levels compared with placebo. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00325195.
Copula Bayesian Networks

We present the Copula Bayesian Network model for representing multivariate continuous distributions, while taking advantage of the relative ease of estimating univariate distributions. Using a novel copula-based reparameterization of a conditional density, joined with a graph that encodes independencies, our model offers great flexibility in modeling high-dimensional densities, while maintaining control over the form of the univariate marginals. We demonstrate the advantage of our framework for generalization over standard Bayesian networks as well as tree structured copula models for varied real-life domains that are of substantially higher dimension than those typically considered in the copula literature.
High throughput screening of disulfide‐containing proteins in a complex mixture

The formation of disulfide bonds between cysteine residues is crucial for the stabilization of native protein structures and, thus, determination of disulfide linkages is an important facet of protein structural characterization. Nonetheless, the identification of disulfide bond linkages remains a significant analytical challenge, particularly in large proteins with complex disulfide patterns. Herein, we have developed a new LC/MS strategy for rapid screening of disulfides in an intact protein mixture after a straightforward reduction step with tris(2‐carboxyethyl)phosphine. LC/MS analysis of reduced and nonreduced protein mixtures quickly revealed disulfide‐containing proteins owing to a 2 Da mass increase per disulfide reduction and, subsequently, the total number of disulfide bonds in the intact proteins could be determined. We have demonstrated the effectiveness of this method in a protein mixture composed of both disulfide‐containing and disulfide‐free proteins. Our method is simple (no need for proteolytic digestion, alkylation, or the removal of reducing agents prior to MS analysis), high throughput (fast on‐line LC/MS analysis), and reliable (no S–S scrambling), underscoring its potential as a rapid disulfide screening method for proteomics applications.
Analysis and interpretation of drug testing results from patients on chronic pain therapy: a clinical laboratory perspective

Abstract Background: Recent guidelines recommend monitoring for opioid and drug use in patients with chronic pain to detect use of undisclosed or illicit substances, and to determine compliance with prescribed medications. We examined the technical and clinical impact of drug testing for patients on chronic pain therapy in our clinical laboratory. Methods: Testing volumes were obtained for 4 years. Volumes from three recent months were also examined in detail to determine average turnaround time, assay performance (i.e., number of positive screening and confirmatory tests and testing discrepancies) and consistency of patient results with medication history. Results: Our testing volume continues to grow significantly, especially in the primary care setting, with an average yearly increase of 34%. Approximately 70% of patients confirmed positive for an opioid. Other drugs were positive in <30% of patients. Twenty-nine percent of patients tested positive for a medication without a prescription. Overall, the compliance rate was 85% indicating that 15% of patients had negative test results despite being prescribed a chronic pain medication. Conclusions: Clinical laboratories should consider the impact of these guidelines and examine options to optimize testing such as limiting or modifying the test panel. Clin Chem Lab Med 2009;47:971–6.
Gradient-Based Optimization of Kernel-Target Alignment for Sequence Kernels Applied to Bacterial Gene Start Detection

Biological data mining using kernel methods can be improved by a task-specific choice of the kernel function. Oligo kernels for genomic sequence analysis have proven to have a high discriminative power and to provide interpretable results. Oligo kernels that consider subsequences of different lengths can be combined and parameterized to increase their flexibility. For adapting these parameters efficiently, gradient-based optimization of the kernel-target alignment is proposed. The power of this new, general model selection procedure and the benefits of fitting kernels to problem classes are demonstrated by adapting oligo kernels for bacterial gene start detection
High-Fidelity Visual Long-Term Memory within an Unattended Blink of an Eye

What is stored in long-term memory from current sensations is a question that has attracted considerable interest. Over time, several prominent theories have consistently proposed that only attended sensory information leaves a durable memory trace whereas unattended information is not stored beyond the current moment, an assumption that seems to be supported by abundant empirical evidence. Here we show, by using a more sensitive memory test than in previous studies, that this is actually not true. Observers viewed a rapid stream of real-world object pictures overlapped by words (presentation duration per stimulus: 500 ms, interstimulus interval: 200 ms), with the instruction to attend to the words and detect word repetitions, without knowing that their memory would be tested later. In a surprise two-alternative forced-choice recognition test, memory for the unattended object pictures was tested. Memory performance was substantially above chance, even when detailed feature knowledge was necessary for correct recognition, even when tested 24 h later, and even although participants reported that they do not have any memories. These findings suggests that humans have the ability to store at high speed detailed copies of current visual stimulations in long-term memory independently of current intentions and the current attentional focus.
Constitutive K-RasG12D Activation of ERK2 Specifically Regulates 3D Invasion of Human Pancreatic Cancer Cells via MMP-1

Pancreatic ductal adenocarcinomas (PDAC) are highly invasive and metastatic neoplasms commonly unresponsive to current drug therapy. Overwhelmingly, PDAC harbors early constitutive, oncogenic mutations in K-RasG12D that exist prior to invasion. Histologic and genetic analyses of human PDAC biopsies also exhibit increased expression of extracellular signal-regulated kinase (ERK) 1/2 and proinvasive matrix metalloproteinases (MMP), indicators of poor prognosis. However, the distinct molecular mechanisms necessary for K-Ras/ERK1/2 signaling and its influence on MMP-directed stromal invasion in primary human pancreatic ductal epithelial cells (PDEC) have yet to be elucidated in three-dimensions. Expression of oncogenic K-RasG12D alone in genetically defined PDECs reveals increased invadopodia and epithelial-to-mesenchymal transition markers, but only when cultured in a three-dimensional model incorporating a basement membrane analog. Activation of ERK2, but not ERK1, also occurs only in K-RasG12D–mutated PDECs cultured in three-dimensions and is a necessary intracellular signaling event for invasion based upon pharmacologic and short hairpin RNA (shRNA) inhibition. Increased active invasion of K-RasG12D PDECs through the basement membrane model is associated with a specific microarray gene expression signature and induction of MMP endopeptidases. Specifically, MMP-1 RNA, its secreted protein, and its proteolytic cleavage activity are amplified in K-RasG12D PDECs when assayed by real-time quantitative PCR, ELISA, and fluorescence resonance energy transfer (FRET). Importantly, shRNA silencing of MMP-1 mimics ERK2 inhibition and disrupts active, vertical PDEC invasion. ERK2 isoform and MMP-1 targeting are shown to be viable strategies to attenuate invasion of K-RasG12D–mutated human pancreatic cancer cells in a three-dimensional tumor microenvironment. Mol Cancer Res; 10(2); 183–96. ©2011 AACR.
Requirement Gathering for small Projects using Agile Methods

Gathering, understanding and managing requirements is a key factor to the success of a software development effort. Requirement engineering is a critical task in all development methods including the agile development method. There are several requirement techniques available for requirement gathering which can be used with agile development methods. These techniques concentrates on a continuous interaction with the customer to address the evolution of requirements, changing requirements, prioritizing requirements and delivers the most important functionalities first. This article presents an overview of agile software development methods and a best requirement elicitation technique used for requirement capturing. We present an application case of requirement gathering process by using User stories for webbased, cost-effective and efficient software (ISODTA- ISO documentation teaching automation) which automates the ISO documentation of teaching process at the institution SNGIST using SCRUM, an agile software development methodology.
TapDance: End-to-Middle Anticensorship without Flow Blocking

In response to increasingly sophisticated state-sponsored Internet censorship, recent work has proposed a new approach to censorship resistance: end-to-middle proxying. This concept, developed in systems such as Telex, Decoy Routing, and Cirripede, moves anticensorship technology into the core of the network, at large ISPs outside the censoring country. In this paper, we focus on two technical obstacles to the deployment of certain end-to-middle schemes: the need to selectively block flows and the need to observe both directions of a connection. We propose a new construction, TapDance, that removes these requirements. TapDance employs a novel TCP-level technique that allows the anticensorship station at an ISP to function as a passive network tap, without an inline blocking component. We also apply a novel steganographic encoding to embed control messages in TLS ciphertext, allowing us to operate on HTTPS connections even under asymmetric routing. We implement and evaluate a TapDance prototype that demonstrates how the system could function with minimal impact on an ISP's network operations.
Type III Effector Diversification via Both Pathoadaptation and Horizontal Transfer in Response to a Coevolutionary Arms Race

The concept of the coevolutionary arms race holds a central position in our understanding of pathogen–host interactions. Here we identify the molecular mechanisms and follow the stepwise progression of an arms race in a natural system. We show how the evolution and function of the HopZ family of type III secreted effector proteins carried by the plant pathogen Pseudomonas syringae are influenced by a coevolutionary arms race between pathogen and host. We surveyed 96 isolates of P. syringae and identified three homologs (HopZ1, HopZ2, and HopZ3) distributed among ∼45% of the strains. All alleles were sequenced and their expression was confirmed. Evolutionary analyses determined that the diverse HopZ1 homologs are ancestral to P. syringae, and have diverged via pathoadaptive mutational changes into three functional and two degenerate forms, while HopZ2 and HopZ3 have been brought into P. syringae via horizontal transfer from other ecologically similar bacteria. A PAML selection analysis revealed that the C terminus of HopZ1 is under strong positive selection. Despite the extensive genetic variation observed in this family, all three homologs have cysteine–protease activity, although their substrate specificity may vary. The introduction of the ancestral hopZ1 allele into strains harboring alternate alleles results in a resistance protein-mediated defense response in their respective hosts, which is not observed with the endogenous allele. These data indicate that the P. syringae HopZ family has undergone allelic diversification via both pathoadaptive mutational changes and horizontal transfer in response to selection imposed by the host defense system. This genetic diversity permits the pathogen to avoid host defenses while still maintaining a virulence-associated protease, thereby allowing it to thrive on its current host, while simultaneously impacting its host range.
Confidence Limit Analysis of Water Distribution Systems Based on a Least Squares Loop Flows State Estimation Technique

This paper presents a novel algorithm for uncertainty quantification in water distribution systems, which is termed also Confidence Limit Analysis (CLA), in the context of a Least Squares (LS) state estimator based on the loop corrective flows and the variation of nodal demands as state variables. The confidence limits predicted with the novel algorithm called Error Maximization (EM) method are evaluated with respect to two other more established CLA algorithms based on an Experimental Sensitivity Matrix (ESM) and on a sensitivity matrix obtained with the LS nodal heads equations state estimator. The predicted confidence limits show that the novel EM algorithm is comparable to the other CLA algorithms shown in the paper and due to its computational efficiency renders it suitable for online decision support systems for water distribution systems.
The full greenhouse gas balance of an abandoned peat meadow

Abstract. Globally, peat lands are considered to be a sink of CO2, but a source when drained. Additionally, wet peat lands are thought to emit considerable amounts of CH4 and N2O. Hitherto, reliable and integrated estimates of emissions and emission factors for this type of land cover have been lacking and the effects of wetland restoration on methane emissions have been poorly quantified. In this paper we estimate the full greenhouse gas (GHG) balance of a restored natural peat land by determining the fluxes of CO2, CH4 and N2O through atmosphere and water, while accounting for the different Global Warming Potentials (GWP's). The site is an abandoned agricultural peat meadow, which has been converted into a wetland nature reserve ten years ago, after which the water level was raised. GHG fluxes were measured continuously with an eddy covariance system (CO2) and flux chamber measurements (CH4 and N2O). Meteorological and hydrological measurements were collected as well. With growing seasons of respectively 192, 168 and 129 days, the annual net ecosystem exchange of CO2 (NEE) was −446+±83 g C m−2 yr−1 for 2004, −311±58 g C m−2 yr−1 for 2005 and −232±57 g m−2 yr−1 for 2006. Ecosystem respiration (Reco) was estimated as 869±668 g C m−2 yr−1 for 2004, 866±666 g C m−2 yr−1 for 2005 and 924±711 g C m−2 yr−1 for 2006. CH4 emissions from the saturated land and water surfaces were high compared to the relatively dry land. Annual weighted CH4 emissions were 31.27±20.40 g C m−2 yr−1 for 2005 and 32.27±21.08 g C m−2 yr−1 for 2006. N2O fluxes were too low to be of significance. The water balance of the area was dominated by precipitation and evapotranspiration and therefore fluxes of carbon and CH4 through seepage, infiltration and drainage were relatively small (17.25 g C m−2 yr−1). The carbon-balance consisted for the largest part of CO2 uptake, CO2 respiration and CH4 emission from water saturated land and water. CO2 emission has decreased significantly as result of the raised water table, while CH4 fluxes have increased. In GWP's the area was a small net GHG sink given as CO2-equiv. of −86 g m−2 yr−1 (over a 100-year period).
Mechanisms of mindfulness: Rumination and self-compassion

Abstract Why do more mindful individuals tend to be less depressed? We hypothesized (1) that mindfulness is associated with depressive symptoms both via the path of lower levels of rumination and higher levels of self-compassion and (2) that the path via self-compassion would explain variance beyond that which could be explained by rumination. Undergraduate students (N = 277) completed the Five Facet Mindfulness Questionnaire, the Rumination subscale of the Rumination-Reflection Questionnaire, the Self-Compassion Scale, and the depression subscale of the symptom checklist-90 revised (SCL-90-R-dep). Results showed that mindfulness was associated with depressive symptoms both via the pathway of lower levels of rumination and via the pathway of higher levels of self-compassion. Both pathways were found to predict unique variance in depressive symptoms beyond that which could be explained by the other pathway. This suggests that one needs to consider the influence of mindfulness on both rumination and on self-compassion in order to fully understand why mindful individuals tend to be less depressed.
Understanding Employee Responses to Stressful Information Security Requirements: A Coping Perspective

We use coping theory to explore an underlying relationship between employee stress caused by burdensome, complex, and ambiguous information security requirements (termed "security-related stress" or SRS) and deliberate information security policy (ISP) violations. Results from a survey of 539 employee users suggest that SRS engenders an emotion-focused coping response in the form of moral disengagement from ISP violations, which in turn increases one's susceptibility to this behavior. Our multidimensional view of SRS—comprised of security-related overload, complexity, and uncertainty—offers a new perspective on the workplace environment factors that foster noncompliant user behavior and inspire cognitive rationalizations of such behavior. The study extends technostress research to the information systems security domain and provides a theoretical framework for the influence of SRS on user behavior. For practitioners, the results highlight the incidence of SRS in organizations and suggest potential mechanisms to counter the stressful effects of information security requirements.