Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of Cryptosporidium parvum Active Chemical Series by Repurposing the Open Access Malaria Box

ABSTRACT The apicomplexan parasites Cryptosporidium parvum and Cryptosporidium hominis are major etiologic agents of human cryptosporidiosis. The infection is typically self-limited in immunocompetent adults, but it can cause chronic fulminant diarrhea in immunocompromised patients and malnutrition and stunting in children. Nitazoxanide, the current standard of care for cryptosporidiosis, is only partially efficacious for children and is no more effective than a placebo for AIDS patients. Unfortunately, financial obstacles to drug discovery for diseases that disproportionately affect low-income countries and technical limitations associated with studies of Cryptosporidium biology impede the development of better drugs for treating cryptosporidiosis. Using a cell-based high-throughput screen, we queried the Medicines for Malaria Venture (MMV) Open Access Malaria Box for activity against C. parvum. We identified 3 novel chemical series derived from the quinolin-8-ol, allopurinol-based, and 2,4-diamino-quinazoline chemical scaffolds that exhibited submicromolar potency against C. parvum. Potency was conserved in a subset of compounds from each scaffold with varied physicochemical properties, and two of the scaffolds identified exhibit more rapid inhibition of C. parvum growth than nitazoxanide, making them excellent candidates for further development. The 2,4-diamino-quinazoline and allopurinol-based compounds were also potent growth inhibitors of the related apicomplexan parasite Toxoplasma gondii, and a good correlation was observed in the relative activities of the compounds in the allopurinol-based series against T. gondii and C. parvum. Taken together, these data illustrate the utility of the Open Access Malaria Box as a source of both potential leads for drug development and chemical probes to elucidate basic biological processes in C. parvum and other apicomplexan parasites.
Encoding of tensile stress and strain during stretch by muscle mechano‐nociceptors

Groups III and IV muscle mechano‐nociceptors (MNs) can be stimulated during noxious stretch, as may occur during hyperextension of a joint. However, the mechanical state (characterized by stress and strain) encoded by MNs during stretch has not previously been determined. The current study used an ex vivo gracilis muscle–nerve preparation in a rat model to apply either a uniform uniaxial or pseudo–shear‐loading paradigm. Single mechanically sensitive group III or IV MNs were mechanically stimulated while plane stress and strain were measured at the location of the MN's receptive field. Linear regression was used to evaluate the relationships between neural response and mechanical stress and strain. The mean neural response (threshold, 47.2 kPa; sensitivity, 0.05 Hz/kPa) was highly correlated to tensile stress, tensile strain, and in‐plane compressive strain but was significantly and substantially less correlated with shear strain. Although the overall stress and strain relationship was nonlinear, it was reasonably linear (r2 = 0.92) for levels suprathreshold for MNs. Hence, at tensile loads sufficient to stimulate MNs, the muscle was acting as a pseudo‐elastic tissue. Thus, muscle MNs encode noxious stretch differently than compression and exhibit different encoding of stretch than cutaneous MNs. Muscle Nerve 30: 216–224, 2004
Restoration of degraded forest ecosystem through non-forestry livelihood supports: experience from the Chunati Wildlife Sanctuary in Bangladesh

ABSTRACT Lack of non-forestry income sources for the forest-dependent community was one of the major causes of continued biodiversity loss in Chunati Wildlife Sanctuary (CWS). A livelihood support program was implemented from July 2012 through June 2015 to reduce people's forest-dependence for their livelihoods. We evaluated the efficacy of this program in enhancing the biodiversity health of CWS. An Ordinary Least Square regression framework was used to estimate the difference in difference of the income between the control and the treatment households. Alongside, the biodiversity attributes of the CWS were measured in 2012 and 2015 and were compared. The intervention increased a treatment household's monthly non-forestry income by BDT11,781 and decreased its monthly forest income by BDT2128. In contrast, with increased natural regeneration of 8.43%, 12 out of the 16 major species at CWS showed increased importance value index (IVI). The IVI increased by 48.03% for Acacia auriculiformis and decreased by 56.30% and 31.76% for Dipterocarpus turbinatus and Tectona grandis, respectively. As confirmed by the households, this biodiversity improvement could be attributed to the livelihood intervention program at CWS. Continued monitoring is important to sustain the successes of the program.
Adrenoleukodystrophy: subcellular localization and degradation of adrenoleukodystrophy protein (ALDP/ABCD1) with naturally occurring missense mutations

Mutation in the X‐chromosomal adrenoleukodystrophy gene (ALD; ABCD1) leads to X‐linked adrenoleukodystrophy (X‐ALD), a severe neurodegenerative disorder. The encoded adrenoleukodystrophy protein (ALDP/ABCD1) is a half‐size peroxisomal ATP‐binding cassette protein of 745 amino acids in humans. In this study, we chose nine arbitrary mutant human ALDP forms (R104C, G116R, Y174C, S342P, Q544R, S606P, S606L, R617H, and H667D) with naturally occurring missense mutations and examined the intracellular behavior. When expressed in X‐ALD fibroblasts lacking ALDP, the expression level of mutant His‐ALDPs (S606L, R617H, and H667D) was lower than that of wild type and other mutant ALDPs. Furthermore, mutant ALDP‐green fluorescence proteins (S606L and H667D) stably expressed in CHO cells were not detected due to rapid degradation. Interestingly, the wild type ALDP co‐expressed in these cells also disappeared. In the case of X‐ALD fibroblasts from an ALD patient (R617H), the mutant ALDP was not detected in the cells, but appeared upon incubation with a proteasome inhibitor. When CHO cells expressing mutant ALDP‐green fluorescence protein (H667D) were cultured in the presence of a proteasome inhibitor, both the mutant and wild type ALDP reappeared. In addition, mutant His‐ALDP (Y174C), which has a mutation between transmembrane domain 2 and 3, did not exhibit peroxisomal localization by immunofluorescense study. These results suggest that mutant ALDPs, which have a mutation in the COOH‐terminal half of ALDP, including S606L, R617H, and H667D, were degraded by proteasomes after dimerization. Further, the region between transmembrane domain 2 and 3 is important for the targeting of ALDP to the peroxisome.
Multiagent Reinforcement Learning for Multi-Robot Systems: A Survey

Multiagent reinforcement learning for multirobot systems is a challenging issue in both robotics and artificial intelligence. With the ever increasing interests in theoretical researches and practical applications, currently there have been a lot of efforts towards providing some solutions to this challenge. However, there are still many difficulties in scaling up the multiagent reinforcement learning to multi-robot systems. The main objective of this paper is to provide a survey, though not completely on the multiagent reinforcement learning in multi-robot systems. After reviewing important advances in this field, some challenging problems and promising research directions are analyzed. A concluding remark is made from the perspectives of the authors.
Physiologically Based Pharmacokinetic Modeling to Predict Transporter-Mediated Clearance and Distribution of Pravastatin in Humans

Hepatobiliary excretion mediated by transporters, organic anion-transporting polypeptide (OATP) 1B1 and multidrug resistance-associated protein (MRP) 2, is the major elimination pathway of an HMG-CoA reductase inhibitor, pravastatin. The present study examined the effects of changes in the transporter activities on the systemic and liver exposure of pravastatin using a physiologically based pharmacokinetic model. Scaling factors, determined by comparing in vivo and in vitro parameters of pravastatin in rats for the hepatic uptake and canalicular efflux, were obtained. The simulated plasma and liver concentrations and biliary excretion profiles were very close to the observed data in rats under linear and nonlinear conditions. In vitro parameters, determined in human cryopreserved hepatocytes and canalicular membrane vesicles, were extrapolated to in vivo parameters using the scaling factors obtained in rats. The simulated plasma concentrations of pravastatin were close to the reported values in humans. Sensitivity analyses showed that changes in the hepatic uptake ability altered the plasma concentration of pravastatin markedly but had a minimal effect on the liver concentration, whereas changes in the ability of canalicular efflux altered the liver concentration of pravastatin markedly but had a small effect on the plasma concentration. In conclusion, the model allows the prediction of the disposition of pravastatin in humans. The present study suggests that changes in the OATP1B1 activities may have a small and a large impact on the therapeutic efficacy and side effect (myopathy) of pravastatin, respectively, whereas those in the MRP2 activities may have opposite impacts (i.e., large and small impacts on the therapeutic efficacy and side effect).
Enhancement of ELDA Tracker Based on CNN Features and Adaptive Model Update

Appearance representation and the observation model are the most important components in designing a robust visual tracking algorithm for video-based sensors. Additionally, the exemplar-based linear discriminant analysis (ELDA) model has shown good performance in object tracking. Based on that, we improve the ELDA tracking algorithm by deep convolutional neural network (CNN) features and adaptive model update. Deep CNN features have been successfully used in various computer vision tasks. Extracting CNN features on all of the candidate windows is time consuming. To address this problem, a two-step CNN feature extraction method is proposed by separately computing convolutional layers and fully-connected layers. Due to the strong discriminative ability of CNN features and the exemplar-based model, we update both object and background models to improve their adaptivity and to deal with the tradeoff between discriminative ability and adaptivity. An object updating method is proposed to select the “good” models (detectors), which are quite discriminative and uncorrelated to other selected models. Meanwhile, we build the background model as a Gaussian mixture model (GMM) to adapt to complex scenes, which is initialized offline and updated online. The proposed tracker is evaluated on a benchmark dataset of 50 video sequences with various challenges. It achieves the best overall performance among the compared state-of-the-art trackers, which demonstrates the effectiveness and robustness of our tracking algorithm.
Some Aspects of Speciation of Mercury in a Water Environment

Extreme toxicity of some species of mercury, the ability of this element to bioaccumulate in particular in fish meat, and the known cases of lethal poisoning by mercury have drawn particular attention to this element's presence in the natural environment. Due to the relatively long time of its presence in the air, elemental mercury can be transported over large distances, hence the presence of mercury of anthropogenic origin is detected practically all over the world. Apart from the elemental mercury, the main species of mercury in water are Hg(II) and mercury-organic species, in particular methylmercury. The latter undergoes strong bioaccumulation in living organisms and concentration in the trophic chains. That is why the relative concentration of mercury in organisms is determined by its presence in water. The concentration of mercury in water is related to the processes of methylation and demethylation, influenced by biotic and abiotic factors such as the activity of microogranisms, access to oxygen, illumination, temperature, pH and others. Despite intense studies, full and reliable recognition of the ecological and health effects of pollution by this toxic metal is still impossible. The aim of this paper is to present the problems related to speciation of mercury, and describe some conversion and migration processes of mercury in the water environment.
A simple method suitable to study de novo root organogenesis

De novo root organogenesis is the process in which adventitious roots regenerate from detached or wounded plant tissues or organs. In tissue culture, appropriate types and concentrations of plant hormones in the medium are critical for inducing adventitious roots. However, in natural conditions, regeneration from detached organs is likely to rely on endogenous hormones. To investigate the actions of endogenous hormones and the molecular mechanisms guiding de novo root organogenesis, we developed a simple method to imitate natural conditions for adventitious root formation by culturing Arabidopsis thaliana leaf explants on B5 medium without additive hormones. Here we show that the ability of the leaf explants to regenerate roots depends on the age of the leaf and on certain nutrients in the medium. Based on these observations, we provide examples of how this method can be used in different situations, and how it can be optimized. This simple method could be used to investigate the effects of various physiological and molecular changes on the regeneration of adventitious roots. It is also useful for tracing cell lineage during the regeneration process by differential interference contrast observation of β-glucuronidase staining, and by live imaging of proteins labeled with fluorescent tags.
How Tourism Communities Can Change Travel Information Quality

Largely ignored by research, online travel communities have already changed the travel behavior of the younger generation. They retrieve and exchange information prior to travelling and share their experiences afterwards. This paper presents some empirical evidence that the quality of the information retrieved justifies their behavior. The evidence is embedded in a larger framework and a set of hypotheses that establish a relationship between the choice of a travel information system and attributes of information quality. The paper argues that relevant attributes of information quality are timeliness, completeness, structure and personalization. Three studies support our proposition that a traditional discussion-based online tourism community provides more timely, more complete and more personalized information than a commercial guidebook. A major deficiency is particularly their lack of structure, but also the other attributes of information quality can be improved by more advanced online tourism communities. A second section thus proposes that a) Wiki communities improve timeliness, completeness and structure of online communities b) personal spaces improve the structure and the personalization of traditional online tourist communities and c) Mobile communities provide higher quality information than traditional online tourist communities.
Presence of human papillomavirus in extrahepatic biliary atresia.

BACKGROUND In a previous study the human papillomavirus DNA was detected in seven cases of so-called idiopathic neonatal giant cell hepatitis by using nested polymerase chain reaction. The purpose of the present study was to study the prevalence and possible common causes of human papillomavirus-associated idiopathic neonatal giant cell hepatitis and extrahepatic biliary atresia. METHODS Formalin-fixed, paraffin-embedded archival tissues obtained in 18 cases of extrahepatic biliary atresia were studied for human papillomavirus DNA by nested polymerase chain reaction. In addition, in situ hybridization was performed on tissue obtained in 6 cases. RESULTS Tissue in 16 of the 18 cases studied showed amplified human papillomavirus DNA, whereas no human papillomavirus was amplified in any of 30 control samples. Main human papillomaviruses detected were types 6 and 18. Punctate intranuclear positive signals were detected in the hepatocytes after in situ hybridization for human papillomavirus DNA. CONCLUSIONS The high prevalence of human papillomavirus DNA in liver tissue in cases of extrahepatic biliary atresia suggests a strong correlation between this disorder and idiopathic neonatal giant cell hepatitis. It further suggests that this virus may be one of the causative agents in extrahepatic biliary atresia and may represent part of the spectrum of lesions associated with neonatal human papillomavirus-induced hepatic damage.
Dual-Wavelength Linearization of Optically Phase-Modulated Analog Microwave Signals

We demonstrate a new technique for improving the linearity of a microwave photonic signal transmission link. The method employs a single conventional lithium-niobate phase modulator at the transmitter, with two different C-band optical wavelengths that are polarized along orthogonal axes of the modulator. The spurious-free dynamic range is shown to improve by 15 dB compared to a single-wavelength unlinearized system. Unlike earlier schemes that require continuous control and adjustment at the transmitter in order to maintain linearity, the new method enables all of the linearization to be controlled at the receiver end.
Higher Islet Amyloid Load in Men Than in Women With Type 2 Diabetes Mellitus

Objectives: Type 2 diabetes mellitus is characterized histopathologically by islet amyloid deposits formed from islet amyloid polypeptide. The aim of this study was to investigate sex difference in islet amyloid of type 2 diabetic patients. Methods: Pancreas specimens were collected from 235 autopsies with type 2 diabetes mellitus. Islet amyloid was identified with Congo red stain. The load of islet amyloid deposits was assessed by prevalence (percentage of cases with islet amyloid deposits), frequency (percentage of islets containing amyloid deposits), and severity (percentage of islet area occupied by amyloid deposits). Results: Women (n = 80) and men (n = 155) had similar age of death, duration of diabetes, body mass index, and hemoglobin (Hb)A1c level. Islet amyloid was found in 30.0% of the women and in 44.5% of the men (P = 0.035). None of 9 women younger than 50 years had islet amyloid. Frequency of amyloid-affected islets was 31.5% ± 13.1% in women and 41.1% ± 14.3% in men (P = 0.008). Severity of amyloid-affected islet area was 29.0% ± 12.5% in women and 38.5% ± 14.6% in men (P = 0.007). Conclusions: Sex is a determinant of the development of islet amyloid in type 2 diabetes mellitus. This sex difference in islet amyloid may be related to a potential benefit of female sex hormones.
Subclinical Alterations of Cardiac Mechanics Present Early in the Course of Pediatric Type 1 Diabetes Mellitus: A Prospective Blinded Speckle Tracking Stress Echocardiography Study

Diabetic cardiomyopathy substantially accounts for mortality in diabetes mellitus. The pathophysiological mechanism underlying diabetes-associated nonischemic heart failure is poorly understood and clinical data on myocardial mechanics in early stages of diabetes are lacking. In this study we utilize speckle tracking echocardiography combined with physical stress testing in order to evaluate whether left ventricular (LV) myocardial performance is altered early in the course of uncomplicated type 1 diabetes mellitus (T1DM). 40 consecutive asymptomatic normotensive children and adolescents with T1DM (mean age 11.5 ± 3.1 years and mean disease duration 4.3 ± 3.5 years) and 44 age- and gender-matched healthy controls were assessed using conventional and quantitative echocardiography (strain and strain rate) during bicycle ergometer stress testing. Strikingly, T1DM patients had increased LV longitudinal (p = 0.019) and circumferential (p = 0.016) strain rate both at rest and during exercise (p = 0.021). This was more pronounced in T1DM patients with a longer disease duration (p = 0.038). T1DM patients with serum HbA1c > 9% showed impaired longitudinal (p = 0.008) and circumferential strain (p = 0.005) and a reduced E/A-ratio (p = 0.018). In conclusion, asymptomatic T1DM patients have signs of hyperdynamic LV contractility early in the course of the disease. Moreover, poor glycemic control is associated with early subclinical LV systolic and diastolic impairment.
Behind the wheel: What drives the effects of error handling?

ABSTRACT Existing research comparing error management (a strategy focusing on increasing the positive and decreasing the negative consequences of errors) to error prevention (a strategy focusing on working faultlessly), has identified error management as beneficial for multiple outcomes. Yet, due to various methodological limitations, it is unclear whether the effects previously found are due to error prevention, error management, or both. We examine this in an experimental study with a 2 (error prevention: yes vs. no) × 2 (error management: yes vs. no) factorial design. Error prevention had negative effects on cognition and adaptive transfer performance. Error management alleviated worry and boosted one’s perceived self-efficacy. Overall, the results show that error prevention and error management have unique outcomes on negative affect, self-efficacy, cognition, and performance.
Novel retrotransposed imprinted locus identified at human 6p25

Differentially methylated regions (DMRs) are stable epigenetic features within or in proximity to imprinted genes. We used this feature to identify candidate human imprinted loci by quantitative DNA methylation analysis. We discovered a unique DMR at the 5′-end of FAM50B at 6p25.2. We determined that sense transcripts originating from the FAM50B locus are expressed from the paternal allele in all human tissues investigated except for ovary, in which expression is biallelic. Furthermore, an antisense transcript, FAM50B-AS, was identified to be monoallelically expressed from the paternal allele in a variety of tissues. Comparative phylogenetic analysis showed that FAM50B orthologs are absent in chicken and platypus, but are present and biallelically expressed in opossum and mouse. These findings indicate that FAM50B originated in Therians after divergence from Prototherians via retrotransposition of a gene on the X chromosome. Moreover, our data are consistent with acquisition of imprinting during Eutherian evolution after divergence of Glires from the Euarchonta mammals. FAM50B expression is deregulated in testicular germ cell tumors, and loss of imprinting occurs frequently in testicular seminomas, suggesting an important role for FAM50B in spermatogenesis and tumorigenesis. These results also underscore the importance of accounting for parental origin in understanding the mechanism of 6p25-related diseases.