Miracle-dz/UniFAR-FTUs huggingface dataset:
Repeated Cis-Regulatory Tuning of a Metabolic Bottleneck Gene during Evolution

Abstract Repeated evolutionary events imply underlying genetic constraints that can make evolutionary mechanisms predictable. Morphological traits are thought to evolve frequently through cis-regulatory changes because these mechanisms bypass constraints in pleiotropic genes that are reused during development. In contrast, the constraints acting on metabolic traits during evolution are less well studied. Here we show how a metabolic bottleneck gene has repeatedly adopted similar cis-regulatory solutions during evolution, likely due to its pleiotropic role integrating flux from multiple metabolic pathways. Specifically, the genes encoding phosphoglucomutase activity (PGM1/PGM2), which connect GALactose catabolism to glycolysis, have gained and lost direct regulation by the transcription factor Gal4 several times during yeast evolution. Through targeted mutations of predicted Gal4-binding sites in yeast genomes, we show this galactose-mediated regulation of PGM1/2 supports vigorous growth on galactose in multiple yeast species, including Saccharomyces uvarum and Lachancea kluyveri. Furthermore, the addition of galactose-inducible PGM1 alone is sufficient to improve the growth on galactose of multiple species that lack this regulation, including Saccharomyces cerevisiae. The strong association between regulation of PGM1/2 by Gal4 even enables remarkably accurate predictions of galactose growth phenotypes between closely related species. This repeated mode of evolution suggests that this specific cis-regulatory connection is a common way that diverse yeasts can govern flux through the pathway, likely due to the constraints imposed by this pleiotropic bottleneck gene. Since metabolic pathways are highly interconnected, we argue that cis-regulatory evolution might be widespread at pleiotropic genes that control metabolic bottlenecks and intersections.
Immediate and long-term effects of a team-based quality improvement training programme

Background Although many studies of quality improvement (QI) education programmes report improvement in learners’ knowledge and confidence, the impact on learners’ future engagement in QI activities is largely unknown and few studies report project measures beyond completion of the programme. Method We developed the Academy for Quality and Safety Improvement (AQSI) to prepare individuals, across multiple departments and professions, to lead QI. The 7-month programme consisted of class work and team-based project work. We assessed participants’ knowledge using a multiple choice test and an adapted Quality Improvement Knowledge Assessment Test (QIKAT) before and after the programme. We evaluated participants’ postprogramme QI activity and project status using surveys at 6 and 18 months. Results Over 5 years, 172 individuals and 32 teams participated. Participants had higher multiple choice test (71.9±12.7 vs 79.4±13.2; p<0.001) and adapted QIKAT scores (55.7±16.3 vs 61.8±14.7; p<0.001) after the programme. The majority of participants at 6 months indicated that they had applied knowledge and skills learnt to improve quality in their clinical area (129/148; 87.2%) and to implement QI interventions (92/148; 62.2%). At 18 months, nearly half (48/101; 47.5%) had led other QI projects and many (41/101; 40.6%) had provided QI mentorship to others. Overall, 14 (43.8%) teams had positive postintervention results at AQSI completion and 20 (62.5%) had positive results at some point (ie, completion, 6 months or 18 months after AQSI). Conclusions A team-based QI training programme resulted in a high degree of participants’ involvement in QI activities beyond completion of the programme. A majority of team projects showed improvement in project measures, often occurring after completion of the programme.
The impact of vaccination route on Mycoplasma gallisepticum vaccine efficacy

ABSTRACT Mycoplasma gallisepticum infection can lead to major financial losses for poultry producers. Control of M. gallisepticum infection in the layer industry is generally obtained through vaccination due to the nature of the multi‐aged flocks in the facilities. Live vaccines can provide significant protection from the pathogenic effects of M. gallisepticum infection. However, differing management practices, including vaccination procedures, can lead to significant variations in the efficacy of the same vaccine. The site of vaccine deposition has been shown to be one important factor significantly influencing the vaccination outcome. Previous research has shown that vaccine applied to the eyes or sprayed on the head is significantly more effective than when sprayed on the body. Vaccine application to the eyes, through the nares (nasal), and 2 routes through the oral cavity were studied to further characterize the most efficient route for delivery. Results of this work demonstrate that eye drop vaccination is significantly more effective than nasal vaccination, and vaccine delivered through the oral cavity has a negligible contribution to overall vaccination outcome.
A Framework for Robot Manipulation: Skill Formalism, Meta Learning and Adaptive Control

In this paper we introduce a novel framework for expressing and learning force-sensitive robot manipulation skills. It is based on a formalism that extends our previous work on adaptive impedance control with meta parameter learning and compatible skill specifications. This way the system is also able to make use of abstract expert knowledge by incorporating process descriptions and quality evaluation metrics. We evaluate various state-of-the-art schemes for meta parameter learning and experimentally compare selected ones. Our results clearly indicate that the combination of our adaptive impedance controller with a carefully defined skill formalism significantly reduces the complexity of manipulation tasks even for learning peg-in-hole with submillimeter industrial tolerances. Overall, the considered system is able to learn variations of this skill in under 20 minutes. In fact, experimentally the system was able to perform the learned tasks without visual feedback faster than humans, leading to the first learning-based solution of complex assembly at such real-world performance.
Associations of Circulating 25-Hydroxyvitamin D3 Concentrations With Incident, Sporadic Colorectal Adenoma Risk According to Common Vitamin D–Binding Protein Isoforms

Concentration of 25-hydroxyvitamin D3 (25(OH)D3), the main circulating form of vitamin D, is inversely associated with incident, sporadic colorectal adenoma risk. We investigated whether this association differs by 2 functional variants in the vitamin D-binding protein (DBP) gene, group-specific component (GC), that encode for common protein isoforms Gc1s, Gc1f, and Gc2 linked to differences in vitamin D metabolism. We pooled data (418 patients with adenoma and 524 polyp-free control subjects) from 3 colonoscopy-based case-control studies (Minnesota, 1991-1994; North Carolina, 1994-1997; South Carolina, 2002). We estimated 25(OH)D3-adenoma associations, stratified by DBP isoforms, using multivariable logistic regression. Higher 25(OH)D3 concentrations were inversely associated with colorectal adenoma risk among those with the Gc2 isoform (per 10-ng/mL increase in 25(OH)D3, odds ratio = 0.71, 95% confidence interval: 0.56, 0.90), but not among those with only Gc1 isoforms (odds ratio = 1.07, 95% confidence interval: 0.87, 1.32; P for interaction = 0.03). Thus, the vitamin D-incident, sporadic colorectal adenoma association may differ by common DBP isoforms, and patients with the Gc2 isoform may particularly benefit from maintaining higher circulating 25(OH)D3 concentrations for adenoma prevention.
Trade Intensity Spillover Effects on East Asian Sustainable Economic Growth

This paper has included the exports and imports per unit of labour (trade intensity) in the intensive growth model beside the traditional factors of production such as capital deepening to find out the contribution of total factor productivity per unit of labour (TFP intensity) to the economic growth of the most significant East Asian countries [China, Indonesia, Japan, South Korea (Republic of Korea), Malaysia, Philippines, Singapore and Thailand]. This paper finds out that the impact of trade intensity is positive with little contribution to TFP intensity growth with light contribution of labour productivity to these countries economic growth. These findings showed that most of East Asian productivity is input driven without technological progress to display the spillover effects of the interaction of foreign technology and human capital that should be translated into technology transfer to local firms and advanced skills, with the exception of Japan and South Korea.
Training Convolutional Networks with Web Images

In this thesis we investigate the effect of using web images to build a large scale database to be used along a deep learning method for a classification task. We replicate the ImageNet large scale database (ILSVRC-2012) from images collected from the web using 4 different download strategies varying: the search engine, the query and the image resolution. As a deep learning method, we will choose the Convolutional Neural Network that was very successful with recognition tasks; the AlexNet.
A de novo mutation in PRICKLE1 associated with myoclonic epilepsy and autism spectrum disorder

Abstract Homozygous recessive mutations in the PRICKLE1 gene were first described in three consanguineous families with myoclonic epilepsy. Subsequent studies have identified neurological abnormalities in humans and animal models with both heterozygous and homozygous mutations in PRICKLE1 orthologs. We describe a 7-year-old with a novel de novo missense mutation in PRICKLE1 associated with epilepsy, autism spectrum disorder and global developmental delay.
Postural Effects on the Mental Rotation of Body-Related Pictures: An fMRI Study

This study investigated the embodied effects involved in the mental rotation of pictures of body parts (hands and feet). Blood oxygen level-dependent (BOLD) signals were collected from 18 healthy volunteers who performed mental rotation tasks of rotated drawings of hands under different arm postures. Congruent drawings of hands (those congruent with left-hand posture) evoked stronger activation in the left supplementary motor area (SMA), left precentral gyrus, and left superior parietal lobule (SPL) than did incongruent drawings of hands. Congruent drawings of hands (those congruent with right-hand posture) evoked significant activation in the left inferior parietal lobule (IPL), right SMA, bilateral middle frontal gyrus (MFG), left inferior frontal gyrus (IFG), and bilateral superior frontal gyrus (SFG) compared to that evoked by the incongruent drawings of hands. Similar methodology was implemented with drawings of feet. However, no significant differences in brain activation were observed between congruent and incongruent drawings of feet. This finding suggests that body posture influences body part-related mental rotation in an effector-specific manner. A direct comparison between the medially and laterally rotated drawings revealed activation in the right IPL, left precentral gyrus, bilateral IFG, and bilateral SFG. These results suggest that biomechanical constraints affect the cognitive process of mental rotation.
Metformin Does Not Inhibit Exercise-Induced Lipolysis in Adipose Tissue in Young Healthy Lean Men

Objective: Metformin was shown to exert an antilipolytic action in adipose tissue (AT) that might mediate beneficial effects on lipid metabolism in diabetic patients. However, during exercise, the inhibition of induced lipolysis in AT would limit the energy substrate supply for working muscle. Thus, the aim of this study was to investigate whether metformin exerts inhibitory effect on exercise-induced lipolysis in subcutaneous adipose tissue (SCAT) (Moro et al., 2007) in humans. Approach: Ten healthy lean men underwent two exercise sessions consisting of 60 min of cycling on bicycle ergometer combined with (a) orally administered metformin and (b) metformin locally administered into SCAT. Microdialysis was used to assess lipolysis in situ in SCAT. Glycerol, metformin and lactate were measured in dialysate and plasma by enzyme colorimetric kits and capillary electrophoresis. Results: Metformin levels increased continuously in plasma during 3 h after oral administration, and peaked after 3.5 h (peak concentration 4 μg/ml). Metformin was detected in dialysate outflowing from SCAT and showed a similar time-course as that in plasma with the peak concentration of 1.3 μg/ml. The lipolytic rate in SCAT (assessed as glycerol release) increased in response to exercise (4.3 ± 0.5-fold vs. basal; p = 0.002) and was not suppressed either by local or oral metformin administration. The lactate levels increased in plasma and in dialysate from SCAT after 30–60 min of exercise (3.6-fold vs. basal; p = 0.015; 2.75-fold vs. basal; p = 0.002, respectively). No effect of metformin on lactate levels in SCAT dialysate or in plasma during exercise was observed. Conclusion: Metformin did not reduce the exercise-induced lipolysis in SCAT. This suggests that metformin administration does not interfere with the lipid mobilization and energy substrate provision during physical activity.
Comparison of time to engraftment between autologous patients receiving washed versus non-washed cryopreserved peripheral blood stem cell products

Abstract Washing cryopreserved peripheral blood stem cell (PBSC) products can decrease infusion-related adverse reactions but can also result in cell loss and reduced cell viability. To assess the risk and benefit of washing products, we compared the time to neutrophil and platelet engraftment between autologous patients that received washed products (n = 201) and non-washed products (n = 89). The effect of the other variables, including age, gender, diagnosis, transplant dose, method of stem cell mobilization, and growth factor support regimen post-transplant, was assessed. In multivariate analysis, direct thaw and infusion of non-washed products resulted in significantly faster neutrophil engraftment (p = .003) and platelet engraftment (p = .017) than washed products. The mean neutrophil and platelet engraftment times were 1.07 days faster and 2.27 days faster, respectively. In conclusion, direct thaw and infusion of cryopreserved PBSC without washing results in significantly shorter time to recovery of neutrophils and platelets after autologous transplantation.
The Myth of the Well-Known Client

ABSTRACT A common idiomatic phrase in mental health care is “well known” client, patient, or service user. This phrase is often followed by “to mental health services” or some such, suggesting that a “service” can really know anything. Notwithstanding mental health services, especially public ones are a repository for a lot of information, such as facts about people, their service use, diagnosis, notes and assessments of various kinds; this conglomeration of information is not knowing, any more than a library may be “knowing”. Knowing is a distinctly human activity. This paper will argue that this phrase is arrogant, a signifier of ignorance and ought to be relegated to history or back room banter with phrases like “frequent flyer”, “bed seeker” and other derogatory and objectifying language.
Eosinophilic annular erythema treated with dupilumab

Eosinophilic annular erythema is a rare, benign, recurrent condition characterized by annular skin lesions, tissue eosinophilia, and resistance to a variety of treatments. There are fewer than 30 cases reported in the English literature, 7 of which are in children. We present a case of recurrent eosinophilic annular erythema in an adolescent that was successfully treated with dupilumab, an interleukin‐4 receptor alpha antagonist.
Proximal Phenotyping and Machine Learning Methods to Identify Septoria Tritici Blotch Disease Symptoms in Wheat

Phenotyping with proximal sensors allow high-precision measurements of plant traits both in the controlled conditions and in the field. In this work, using machine learning, an integrated analysis was done from the data obtained from spectroradiometer, infrared thermometer, and chlorophyll fluorescence measurements to identify most predictive proxy measurements for studying Septoria tritici blotch (STB) disease of wheat. The random forest (RF) models for chlorosis and necrosis identified photosystem II quantum yield (QY) and vegetative indices (VIs) associated with the biochemical composition of leaves as the top predictive variables for identifying disease symptoms. The RF model for chlorosis was validated with a validation set (R2: 0.80) and in an independent test set (R2: 0.55). Based on the results, it can be concluded that the proxy measurements for photosystem II, chlorophyll content, carotenoid, and anthocyanin levels and leaf surface temperature can be successfully used to detect STB. Further validation of these results in the field will enable application of these predictive variables for detection of STB in the field.
Genomic Deletion Involving the IMMP2L Gene in Two Cases of Autism Spectrum Disorder

Mutations/deletions of the IMMP2L gene have been associated with different cognitive/behavioral disturbances, including autism spectrum disorders (ASD). The penetrance of these defects is not complete since they often are inherited from a healthy parent. Using array-CGH in a cohort of 37 ASD patients, we found 2 subjects harboring a deletion inside the IMMP2L gene. In both cases, the IMMP2L gene deletion was inherited: from a healthy mother in one case and from a dyslectic father in the other. In the latter family, the IMMP2L deletion was also detected in the patient's brother, who showed delayed language development. In a cohort of 100 normal controls, no deletions including the IMMP2L gene were observed. However, a recent meta-analysis found no association between IMMP2L deletions and ASD. Our data would indicate that deletions involving the IMMP2L gene may contribute to the development of a subgroup of cognitive/behavioral disorders.
Viktoria Plemakova Vehicle Detection Based on Convolutional Neural Networks

Accurate vehicle detection or classification plays an important role in Intelligent Transportations Systems. Ability to detect vehicles in traffic scenes allows analyzing drivers’ behavior as well as detect traffic offenses and accidents. Detection and classification of vehicles is a challenging task due to weather and light conditions and vehicle type diversity. Several solutions use feature extraction algorithms along with support vector machine classifier. However, convolutional neural networks have proved to be potentially more effective. In this thesis, we present a convolutional neural network trained to classify and detect vehicles from multiple angles. Moreover, Fast Fourier Transform is used during data preprocessing. The effect of such preprocessing is examined on the developed vehicle classifier and detector.
A Tropical Approach to Neural Networks with Piecewise Linear Activations

We present a new, unifying approach following some recent developments on the complexity of neural networks with piecewise linear activations. We treat neural network layers with piecewise linear activations, such as Maxout or ReLU units, as polynomials in the $(\max, +)$ (or so-called tropical) algebra. Following up on the work of Montufar et al. (arXiv:1402.1869), this approach enables us to improve their upper bound on linear regions of layers with ReLU or leaky ReLU activations to $\min \left\{ 2^m, 2 \cdot \sum_{j=0}^n \binom{m - 1}{j} \right\}$, where $n, m$ are the number of inputs and outputs, respectively. Additionally, we recover their upper bounds on maxout layers. Our work is parallel to the improvements reported in (arXiv:1711.02114, arXiv:1611.01491), though exclusively under the lens of tropical geometry.
A Synergistic Transcriptional Regulation of Olfactory Genes Drives Blood-Feeding Associated Complex Behavioral Responses in the Mosquito Anopheles culicifacies

Decoding the molecular basis of host seeking and blood feeding behavioral evolution/adaptation in the adult female mosquitoes may provide an opportunity to design new molecular strategy to disrupt human-mosquito interactions. Although there is a great progress in the field of mosquito olfaction and chemo-detection, little is known about the sex-specific evolution of the specialized olfactory system of adult female mosquitoes that enables them to drive and manage the complex blood-feeding associated behavioral responses. A comprehensive RNA-Seq analysis of prior and post blood meal olfactory system of An. culicifacies mosquito revealed a minor but unique change in the nature and regulation of key olfactory genes that may play a pivotal role in managing diverse behavioral responses. Based on age-dependent transcriptional profiling, we further demonstrated that adult female mosquito's chemosensory system gradually learned and matured to drive the host-seeking and blood feeding behavior at the age of 5–6 days. A time scale expression analysis of Odorant Binding Proteins (OBPs) unravels unique association with a late evening to midnight peak biting time. Blood meal-induced switching of unique sets of OBP genes and Odorant Receptors (Ors) expression coincides with the change in the innate physiological status of the mosquitoes. Blood meal follows up experiments further provide enough evidence that how a synergistic and concurrent action of OBPs-Ors may drive “prior and post blood meal” associated complex behavioral events. A dominant expression of two sensory appendages proteins (SAP-1 & SAP2) in the legs of An. culicifacies suggests that this mosquito species may draw an extra advantage of having more sensitive appendages than An. stephensi, an urban malarial vector in the Indian subcontinents. Finally, our molecular modeling analysis predicts crucial amino acid residues for future functional characterization of the sensory appendages proteins which may play a central role in regulating multiple behaviors of An. culicifacies mosquito. SIGNIFICANCE Evolution and adaptation of blood feeding behavior not only favored the reproductive success of adult female mosquitoes but also make them important disease-transmitting vectors. An environmental exposure after emergence may favor the broadly tuned olfactory system of mosquitoes to drive complex behavioral responses. But, how these olfactory derived genetic factors manage female specific “pre and post” blood meal associated complex behavioral responses are not well known. Our findings suggest that a synergistic action of olfactory factors may govern an innate to prime learning strategy to facilitate rapid blood meal acquisition and downstream behavioral activities. A species-specific transcriptional profiling and an in-silico analysis predict that “sensory appendages protein” may be a unique target to design disorientation strategy against the mosquito Anopheles culicifacies.