Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanisms and significance of fungicide resistance

In this review article, we show that occurrence of fungicide resistance is one of the most important issues in modern agriculture. Fungicide resistance may be due to mutations of genes encoding fungicide targets (qualitative fungicide resistance) or to different mechanisms that are induced by sub-lethal fungicide stress. These mechanisms result in different and varying levels of resistance (quantitative fungicide resistance). We discuss whether or not extensive use of fungicides in agricultural environments is related to the occurrence of fungicide resistance in clinical environments. Furthermore, we provide recommendations of how development of fungicide resistant pathogen populations may be prevented or delayed.
A risk assessment example for soil invertebrates using spatially explicit agent‐based models

Current risk assessment methods for measuring the toxicity of plant protection products (PPPs) on soil invertebrates use standardized laboratory conditions to determine acute effects on mortality and sublethal effects on reproduction. If an unacceptable risk is identified at the lower tier, population‐level effects are assessed using semifield and field trials at a higher tier because modeling methods for extrapolating available lower‐tier information to population effects have not yet been implemented. Field trials are expensive, time consuming, and cannot be applied to variable landscape scenarios. Mechanistic modeling of the toxicological effects of PPPs on individuals and their responses combined with simulation of population‐level response shows great potential in fulfilling such a need, aiding ecologically informed extrapolation. Here, we introduce and demonstrate the potential of 2 population models for ubiquitous soil invertebrates (collembolans and earthworms) as refinement options in current risk assessment. Both are spatially explicit agent‐based models (ABMs), incorporating individual and landscape variability. The models were used to provide refined risk assessments for different application scenarios of a hypothetical pesticide applied to potato crops (full‐field spray onto the soil surface [termed “overall”], in‐furrow, and soil‐incorporated pesticide applications). In the refined risk assessment, the population models suggest that soil invertebrate populations would likely recover within 1 year after pesticide application, regardless of application method. The population modeling for both soil organisms also illustrated that a lower predicted average environmental concentration in soil (PECsoil) could potentially lead to greater effects at the population level, depending on the spatial heterogeneity of the pesticide and the behavior of the soil organisms. Population‐level effects of spatial‐temporal variations in exposure were elucidated in the refined risk assessment, using ABMs and population‐level endpoints while yielding outputs that directly address the protection goals. We recommend choosing model outputs that are closely related to specific protection goals, using available toxicity data and accepted fate models to the extent possible in parameterizing models to minimize additional data needs and testing, evaluating, and documenting models following recent guidance. Integr Environ Assess Manag 2016;12:58–66. © 2015 SETAC
The Future of Heart Failure Diagnosis, Therapy, and Management.

Over the past 4 decades, patients with heart failure (HF) have derived substantial benefit from the major advances in our understanding of pathophysiology of the HF syndrome, which have led to evolving treatment paradigms. Morbidity and mortality for patients as documented in clinical trials for HF with reduced ejection fraction (HFrEF) have steadily decreased, and many patients with this syndrome have also enjoyed improved functional capacity and quality of life. However, there are major unmet needs. Hospital discharges with a primary HF diagnosis, an index of population disease burden and economic impact, remain >1 million annually with little change between 2000 and 2010.1 According to the American Heart Association’s Heart and Stroke Facts,2 the prevalence of HF will increase ≈50% between 2012 and 2030, resulting in >8 million people ≥18 years of age with HF.3 This daunting future reflects the increased prevalence of HF as the population ages, acute myocardial infarction survival improves, and HF survival itself increases at rates that exceed our impact to prevent the development of HF. The national and, indeed, international burden of HF reflects a growing component of HF with preserved ejection fraction (HFpEF), for which trials have been neutral, in contrast to the progress for HFrEF. These frustrating trial results reflect our incomplete understanding of the more heterogeneous complex of the HFpEF syndrome, which was only defined as an entity more recently. Knowledge in this area has evolved over the past few years, however, suggesting that positive results may be enabled by more targeted treatments rather than broad-brush interventions and a shift in focus to symptoms and daily quality of life as primary outcomes. In this review, we will use the lessons of the recent past to illuminate pathways forward in how the HF syndrome is conceptualized, how we might better …
Burning off DNA Methylation: New Evidence for Oxygen‐Dependent DNA Demethylation

Where do you stop? Three recent publications have described how the oxidation of 5-methylcytosine by Tet dioxygenases does not stop at the 5-hydroxymethylcytosine (5hmC) state, rather further oxidation of 5hmC is involved in DNA demethylation. The nature of the enzymes involved in this process shed light on the dynamics of epigenetic signaling and its evolutionary origin.
Delivery of plasmid encoding interleukin-12 gene into hepatocytes by conjugated polyethylenimine-based nanoparticles

Abstract In the present investigation, polyethylenimine (PEI) was conjugated with succinic anhydride at four substitution degrees and the efficiency of the modified PEI derivatives in transferring the plasmid encoding interleukin-12 gene was evaluated. The results revealed that the conjugated PEI derivatives enhanced the transfection efficiency by up to 3-fold relative to unmodified PEI, with the highest increase occurring at conjugation degrees around 30%. The results demonstrated the ability of the modified PEI derivatives in condensation of the plasmid into the nanoparticles in the size range of approximately 100 nm. Also, the PEI derivatives exhibited substantial decrease in cell-induced toxicity.
Familial Aggregation of Pure Tone Hearing Thresholds in an Aging European Population

Objective To investigate the familial correlations and intraclass correlation of age-related hearing impairment (ARHI) in specific frequencies. In addition, heritability estimates were calculated. Study Design Multicenter survey in 8 European centers. Subjects One hundred ninety-eight families consisting of 952 family members, screened by otologic examination and structured interviews. Subjects with general conditions, known to affect hearing thresholds or known otologic cause were excluded from the study. Results We detected familial correlation coefficients of 0.36, 0.37, 0.36, and 0.30 for 0.25, 0.5, 1, and 2 kHz, respectively, and correlation coefficients of 0.20 and 0.18 for 4 and 8 kHz, respectively. Variance components analyses showed that the proportion of the total variance attributable to family differences was between 0.32 and 0.40 for 0.25, 0.5, 1, and 2 kHz and below 0.20 for 4 and 8 kHz. When testing for homogeneity between sib pair types, we observed a larger familial correlation between female than male subjects. Heritability estimates ranged between 0.79 and 0.36 across the frequencies. Discussion Our results indicate that there is a substantial shared familial effect in ARHI. We found that familial aggregation of ARHI is markedly higher in the low frequencies and that there is a trend toward higher familial aggregation in female compared with male subjects.
Biological Activity of Thiazole Derivatives on Some Pathogenic Microorganisms

The thiazole derivatives were prepared by the reaction of benzaldehyde derivatives with (2-thiooxamide-5-(p-bromobenzene)-1,3-thiazole) that was readily prepared by heating dithiooxamide with 4-bromophenacylbromide. Within invitro study the the effect of the prepared compounds on the growth of two types of fungi geotrichum cadidum and Trichophyton rubrum and the bacteria Escherichia coli, pseudomonas aeruginosa, Staphylococcus aureus, and Klebsiella pneumoniae was evaluated. Incubation time and concentration were studied to find the optimal conditions for the activity. Compound II with the concentration 20 mg/ml found to be the most active compound toward geotrichum and Trichophyton rubrum. Statistical analysis of the values of colonial diameter shows low percentage error for the studied fungi with regard to incubation time.
Intelligent understanding and wishful thinking: the dangers of epistemological alchemy

BREIMAN, L. , FRIEDMAN, J. H. , OLSHEN, R. A. , and STONE, C. J. 1984. Classification and regression trees. Wadsworth, Belmont, CA. CHRISTENSEN, R. 198 1. Entropy minimax sourcebook: general description. Entropy, Ltd., Lincoln, MA. DIETTERICH, T. G . , LONDON, B. , CLARKSON, K. , and DROMEY, G. 1982. Learning and inductive inference. In The handbook of artificial intelligence. Edited by P. R. Cohen and E. A. Feigenbaum. Kaufmann, Los Altos, CA. HAUSSLER, D. 1986. Quantifying the inductive bias in concept learning. Proceedings of the Fifth National Conference on Artificial Intelligence, Philadelphia, PA, pp. 485 -489. HORVITZ, E. J., HECKERMAN, D. E. , and LANGLOTZ, C. P. 1986. A framework for comparing alternative formalisms for plausible reasoning. Proceedings of the Fifth National Conference on Artificial Intelligence, Philadelphia, PA, pp. 210-214. MICHALSKI, R. S. 1980. Pattern recognition as rule-guided inductive inference. IEEEE Transactions on Pattern Recognition and Machine Inelligence, 2: 349 -361. 1983. A theory and methodology of inductive learning. Artificial Intelligence, 20(2): 11 1 161. Reprinted in Machine learning: an artificial intelligence approach. Edited by R. s . Michalski, J. G. Carbonell, and T. M. Mitchell. Tioga Publishing Co., Palo Alto, CA, pp. 83-134. MICHAISKI, R. S . , and CHILAUSKY, R. L. 1980. Learning by being told and learning from examples: an experimental comparison of the two methods of knowledge acquisition in the context of developing an expert system for soybean disease diagnose. International Journal of Policy Analysis and Information Systems, 4: 125-161. 254 -261. MITCHELL, T. M. 1978. Version spaces: an approach to concept learning. Ph.D. thesis, Stanford University, Stanford, CA. 1980. The need for biases in learning generalizations. Technical Report CBM-TR-117, Department of Computer Science, Rutgers University, New Brunswick, NJ. 1982. Generalization as search. Artificial Intelligence, 21:
Plant immune receptor decoy: Pathogens in their own trap

Microbial pathogens have evolved sophisticated strategies to infect their hosts, often resulting in disease. The host, in turn, can produce novel proteins (receptors or antibodies) that recognize pathogen molecules to trigger defense. Unlike animals, plants do not possess any adaptive immunity to defend themselves against pathogens. Therefore, they rely entirely on their genetic resistance capability (innate immunity) conferred by a family of receptors expressed in individual cells. The plant innate immune system can be divided into two layers of defense. The first, known as pattern-triggered immunity (PTI) leading to basal defense, involves the recognition of microbe-associated molecular patterns (MAMPs) by corresponding plasma membrane pattern-recognition receptors (PRRs). PTI can be suppressed by specific pathogen virulence factors (known as effectors). To detect such pathogen molecules or their interference with host proteins, plants have evolved a second layer of defense, known as effector-triggered immunity (ETI) [1]. ETI is mediated by intracellular nucleotide-binding–leucine-rich repeat receptors (NLRs) that resemble mammalian NLRs [2]. The speed with which microbial populations can produce new effectors places enormous pressure on plant hosts to fight back with genetically new or altered receptor recognition modes.
Hidden leprosy--who is hiding from whom?

Prevalence of registered leprosy cases has fallen substantially, by about 90%, over the last 2 decades. From 5·4 million cases in 1985 to 0·53 million at the beginning of 2003, the achievement is impressive indeed. Globally, the registered prevalence has reached the strategic milestone of less than 1 per 10,000 population. Out of 122 endemic countries, only six in Asia, Africa and the Americas have a prevalence of more than one per 10,000. While prevalence depicts the success side of the programme, when it comes to new case detection the picture is altogether different. The annual number of new cases detected has remained around 500,000 ever since the introduction of MDT. It has not shown a perceptible decline despite the best efforts by the programme. Even in countries that have achieved the magic figure of prevalence less than 1 per 10,000 population, new case detection has not shown any significant downtrend. Ineffective coverage or delay in the introduction of MDT; intensified efforts at case detection, in the name of enhancing MDT coverage, in some countries, through national or subnational leprosy elimination campaigns (LEC); and problems associated with integration of leprosy service into general health such as less than optimal capacity of the medical professionals to diagnose leprosy correctly, could be some of the factors contributing to sustained level of new case detection. One of the reasons for the persistent level of new case detection is ineffective coverage of population resulting in a significant proportion of new cases remaining undetected by the health system. Effective coverage means reaching with MDT service every individual in need without constraints in terms of affordability, acceptability, resource availability, provider quality and physical access. These constraints often render it difficult for the health system to detect all the cases that occur in the community and treat them promptly so that they are cured and have no residual impairment. While increasing attention is given to ‘overdetection’ of cases, ‘underdetection’ is ignored for various reasons. Overdetection is not difficult to validate, is manageable and is attractive to programme managers because of its immediate visible impact, whereas underdetection is rather difficult to estimate and is less appealing to programme managers and therefore has no apparent mandate. While we have some idea about overdetection, there is obvious lack of information on underdetection. Cases that have already occurred and are yet to be detected are commonly referred to as ‘hidden’ cases which can be of two categories: patients with disease who are yet to report to Lepr Rev (04) 75, 303–305
Epistasis in Genetic Algorithms: An Experimental Design Perspective

In an earlier paper we examined the relationship between genetic algorithms (GAs) and traditional methods of experimental design. This was motivated by an investigation into the problems caused by epistasis in the implementation and application of GAs to optimization problems. We showed how this viewpoint enables us to gain further insights into the determination of epistatic effects , and into the value of diierent forms of encoding a problem for a GA solution. We also demonstrated the equivalence of this approach toWalsh transform analysis. In this paper we consider further the question of whether the epistasis metric actually gives a good prediction of the ease or dii-culty of solution of a given problem by a GA. Our original analysis assumed, as does the rest of the related literature, knowledge of the complete solution space. In practice, we only ever sample a fraction of all possible solutions , and this raises signiicant questions which are the subject of the second part of this paper. In order to analyse these questions , we introduce the concept of alias sets, and conclude by discussing some implications for the traditional understanding of how GAs work.
Bone formation in sinus augmentation procedures using autologous bone, porcine bone, and a 50 : 50 mixture: a human clinical and histological evaluation at 2 months.

OBJECTIVES The aim of this study was to perform a 2 months clinical and histological comparison of autologous bone, porcine bone, and a 50 : 50 mixture in maxillary sinus augmentation procedures. MATERIALS AND METHODS A total of 10 consecutive patients, undergoing two-stage sinus augmentation procedures using 100% autologous bone (Group A), 100% porcine bone (Group B), and a 50 : 50 mixture of autologous and porcine bone (Group C) were included in this study. After a 2-month healing period, at the time of implant insertion, clinical evaluation was performed and bone core biopsies were harvested and processed for histological analysis. RESULTS The postoperative healing was uneventful regardless of the materials used for the sinus augmentation procedures. The histomorphometrical analysis revealed comparable percentages of newly formed bone, marrow spaces, and residual grafted material in the three groups. CONCLUSION The clinical and histological results of this study indicated that porcine bone alone or in combination with autologous bone are biocompatible and osteoconductive materials and can be successfully used in sinus augmentation procedures.
Infrastructure-to-vehicle cooperative communications with decode-and-forward relaying

In this paper, we consider infrastructure-to-vehicle cooperative communications in which roadside access points use vehicles as relaying terminals. This can be particularly useful in suburban or remote areas where the frequent deployment of roadside access points is not either possible or cost-effective. For the doubly-selective vehicular channel under consideration, we employ a precoded cooperative transmission technique to extract the underlying rich multipath-Doppler-spatial diversity. Under the assumption of decode-and-forward relaying, we derive a pairwise error probability expression and demonstrate the achievable diversity gains. We further provide Monte Carlo simulations to confirm the analytical derivations and provide insight into the error rate performance of infrastructure-to-vehicle cooperative communications.
Aldosterone increases KCa1.1 (BK) channel‐mediated colonic K+ secretion

Mammalian K+ homeostasis results from highly regulated renal and intestinal absorption and secretion, which balances the unregulated K+ intake. Aldosterone is known to enhance both renal and colonic K+ secretion. In mouse distal colon K+ secretion occurs exclusively via luminal KCa1.1 (BK) channels. Here we investigate if aldosterone stimulates colonic K+ secretion via BK channels. Luminal Ba2+ and iberiotoxin (IBTX)‐sensitive electrogenic K+ secretion was measured in Ussing chambers. In vivo aldosterone was augmented via a high K+ diet. High K+ diet led to a 2‐fold increase of luminal Ba2+ and IBTX‐sensitive short‐circuit current in distal mouse colonic mucosa. This effect was absent in BK α‐subunit‐deficient (BK−/−) mice. The resting and diet‐induced K+ secretion was stimulated by luminal ionomycin. In BK−/− mice luminal ionomycin did not stimulate K+ secretion. In vitro addition of aldosterone likewise triggered a 2‐fold increase in K+ secretion, which was inhibited by the mineralocorticoid receptor antagonist spironolactone and the BK channel blocker IBTX. Semi‐quantification of mRNA from colonic crypts showed up‐regulation of BK α‐ and β2‐subunits in high K+ diet mice. The BK channel could be detected luminally in colonic crypt cells by immunohistochemistry. The expression level of the channel in the luminal membrane was strongly up‐regulated in K+‐loaded animals. Taken together, these data strongly suggest that aldosterone‐induced K+ secretion occurs via increased expression of luminal BK channels.
Chromatin Fiber Dynamics under Tension and Torsion

Genetic and epigenetic information in eukaryotic cells is carried on chromosomes, basically consisting of large compact supercoiled chromatin fibers. Micromanipulations have recently led to great advances in the knowledge of the complex mechanisms underlying the regulation of DNA transaction events by nucleosome and chromatin structural changes. Indeed, magnetic and optical tweezers have allowed opportunities to handle single nucleosomal particles or nucleosomal arrays and measure their response to forces and torques, mimicking the molecular constraints imposed in vivo by various molecular motors acting on the DNA. These challenging technical approaches provide us with deeper understanding of the way chromatin dynamically packages our genome and participates in the regulation of cellular metabolism.
Clinical experience with fixed bimonthly aflibercept dosing in treatment-experienced patients with neovascular age-related macular degeneration

Purpose To evaluate the durability of fixed bimonthly dosing of intravitreal aflibercept for neovascular age-related macular degeneration. Methods Records of 16 patients were retrospectively reviewed. Patients received three initial 2.0 mg monthly doses of aflibercept then 8-weekly doses according to the product label. Best-corrected visual acuity (Early Treatment Diabetic Retinopathy Study [ETDRS] letters), central macular thickness, fluid on optical coherence tomography, and pigment epithelial detachment (PED) were measured. Results Prior to starting aflibercept, 13 patients had subretinal fluid (SRF), five had intraretinal fluid (IRF), four had PED, and baseline visual acuity (VA) was 62 approximate ETDRS letters. Following the monthly dosing, seven patients had no improvement or decreased VA, ten patients still had SRF/IRF, and PED had worsened in one patient. At Visit 4, an average of 6.8 weeks after Visit 3, VA had decreased in seven patients, SRF/IRF had increased in 12 patients, and PED had returned in all patients who initially responded. Based on the presence of fluid after the initial monthly injections, 12 patients could not be extended to fixed bimonthly dosing. Conclusion This study adds to the growing body of evidence on the need for flexible dosing schedules for the personalized treatment of neovascular age-related macular degeneration.