Miracle-dz/UniFAR-FTUs huggingface dataset:
Deep learning for computational chemistry

The rise and fall of artificial neural networks is well documented in the scientific literature of both computer science and computational chemistry. Yet almost two decades later, we are now seeing a resurgence of interest in deep learning, a machine learning algorithm based on multilayer neural networks. Within the last few years, we have seen the transformative impact of deep learning in many domains, particularly in speech recognition and computer vision, to the extent that the majority of expert practitioners in those field are now regularly eschewing prior established models in favor of deep learning models. In this review, we provide an introductory overview into the theory of deep neural networks and their unique properties that distinguish them from traditional machine learning algorithms used in cheminformatics. By providing an overview of the variety of emerging applications of deep neural networks, we highlight its ubiquity and broad applicability to a wide range of challenges in the field, including quantitative structure activity relationship, virtual screening, protein structure prediction, quantum chemistry, materials design, and property prediction. In reviewing the performance of deep neural networks, we observed a consistent outperformance against non‐neural networks state‐of‐the‐art models across disparate research topics, and deep neural network‐based models often exceeded the “glass ceiling” expectations of their respective tasks. Coupled with the maturity of GPU‐accelerated computing for training deep neural networks and the exponential growth of chemical data on which to train these networks on, we anticipate that deep learning algorithms will be a valuable tool for computational chemistry. © 2017 Wiley Periodicals, Inc.
The use of shared medication record as part of medication reconciliation at hospital admission is feasible.

INTRODUCTION Medication reconciliation improves congruence in cross sectional patient courses. Our regional electronic medical record (EMR) integrates the shared medication record (SMR) which provides full access to current medication and medication prescriptions for all citizens in Denmark. We studied whether our SMR integration could facilitate medication reconciliation. MATERIAL AND METHODS Patients admitted to the emergency department for hospitalization were randomised to consultation using EMR with or without the integrated SMR access. Observed time used for medication reconciliation was the primary efficacy parameter. RESULTS A total of 62 consecutive patient consultations were randomised including 39 with more than five prescriptions. EMR had data from previous consultations for 46 patients, 59 patients provided information on medication. In all, 18 junior physicians in early postgraduate medical training each participated with a median of three consultations (range 1-9). Time expenditure for medicine reconciliation was 5:27 min.:sec. (range: 2:00-15:37) with access to SMR integration and 4:15 min.:sec. (1:15-12:00) without SMR access. The number of active medicine prescriptions was eight and nine, respectively. Incorporating SMR did not increase the work load. Physicians judged the SMR integration and workflow as being useful. Patients unambiguously sup-ported physicians' use of SMR in this setting. CONCLUSION Integration of information on individuals' medication from a national SMR into a hospital EMR was feasible and useful, and it did not increase time expenditure for medication reconciliation. FUNDING not relevant. TRIAL REGISTRATION not relevant.
Involvement of the orphan nuclear estrogen receptor-related receptor α in osteoclast adhesion and transmigration

The orphan nuclear receptor, estrogen receptor-related receptor α (ERRα) is expressed in osteoblasts and osteoclasts (OCs) and has been proposed to be a modulator of estrogen signaling. To determine the role of ERRα in OC biology, we knocked down ERRα activity by transient transfection of an siRNA directed against ERRα in the RAW264.7 monocyte–macrophage cell line that differentiates into OCs in the presence of receptor activator of nuclear factor κB-ligands and macrophage colony-stimulating factor. In parallel, stable RAW cell lines expressing a dominant-negative form of ERRα and green fluorescent protein (RAW-GFP-ERRαΔAF2) were used. Expression of OC markers was assessed by real-time PCR, and adhesion and transmigration tests were performed. Actin cytoskeletal organization was visualized using confocal microscopy. We found that RAW264.7 cells expressing siRNA directed against ERRα and RAW-GFP-ERRαΔAF2 OCs displayed abnormal spreading, and decreased osteopontin and β3 integrin subunit expression compared with the corresponding control cells. Decreased adhesion and the absence of podosome belts concomitant with abnormal localization of c-src were also observed in RAW-GFP-ERRαΔAF2-derived OCs. In addition, RAW-GFP-ERRαΔAF2-derived OCs failed to transmigrate through osteoblast cell layers. Our data show that the impairment of ERRα function does not alter OC precursor proliferation and differentiation but does alter the adhesion/spreading and migration capacities of mature OCs.
Neuronal Learning of Invariant Object Representation in the Ventral Visual Stream Is Not Dependent on Reward

Neurons at the top of primate ventral visual stream [inferior temporal cortex (IT)] have selectivity for objects that is highly tolerant to variation in the object's appearance on the retina. Previous nonhuman primate (Macaca mulatta) studies suggest that this neuronal tolerance is at least partly supported by the natural temporal contiguity of visual experience, because altering that temporal contiguity can robustly alter adult IT position and size tolerance. According to that work, it is the statistics of the subject's visual experience, not the subject's reward, that instruct the specific images that IT treats as equivalent. But is reward necessary for gating this type of learning in the ventral stream? Here we show that this is not the case—temporal tolerance learning proceeds at the same rate, regardless of reward magnitude and regardless of the temporal co-occurrence of reward, even in a behavioral task that does not require the subject to engage the object images. This suggests that the ventral visual stream uses autonomous, fully unsupervised mechanisms to constantly leverage all visual experience to help build its invariant object representation.
The Evolutionary Potential of Phenotypic Mutations

Errors in protein synthesis, so-called phenotypic mutations, are orders-of-magnitude more frequent than genetic mutations. Here, we provide direct evidence that alternative protein forms and phenotypic variability derived from translational errors paved the path to genetic, evolutionary adaptations via gene duplication. We explored the evolutionary origins of Saccharomyces cerevisiae IDP3 - an NADP-dependent isocitrate dehydrogenase mediating fatty acids ß-oxidation in the peroxisome. Following the yeast whole genome duplication, IDP3 diverged from a cytosolic ancestral gene by acquisition of a C-terminal peroxisomal targeting signal. We discovered that the pre-duplicated cytosolic IDPs are partially localized to the peroxisome owing to +1 translational frameshifts that bypass the stop codon and unveil cryptic peroxisomal targeting signals within the 3’-UTR. Exploring putative cryptic signals in all 3’-UTRs of yeast genomes, we found that other enzymes related to NADPH production such as pyruvate carboxylase 1 (PYC1) might be prone to peroxisomal localization via cryptic signals. Using laboratory evolution we found that these translational frameshifts are rapidly imprinted via genetic single base deletions occurring within the very same gene location. Further, as exemplified here, the sequences that promote translational frameshifts are also more prone to genetic deletions. Thus, genotypes conferring higher phenotypic variability not only meet immediate challenges by unveiling cryptic 3’-UTR sequences, but also boost the potential for future genetic adaptations.
The Relational Health Indices: Reanalysis of a Measure of Relational Quality

Abstract The study examined the component structure of the Relational Health Indices (B. Liang et al., 2002) with a mixed-sex sample of students seeking services at a university counseling center. In contrast to previous findings, results suggested a unidimensional structure for the peer and mentor composites and a 2-component structure for the community composite.
Parallel Pathways for Cross-Modal Memory Retrieval in Drosophila

Memory-retrieval processing of cross-modal sensory preconditioning is vital for understanding the plasticity underlying the interactions between modalities. As part of the sensory preconditioning paradigm, it has been hypothesized that the conditioned response to an unreinforced cue depends on the memory of the reinforced cue via a sensory link between the two cues. To test this hypothesis, we studied cross-modal memory-retrieval processing in a genetically tractable model organism, Drosophila melanogaster. By expressing the dominant temperature-sensitive shibirets1 (shits1) transgene, which blocks synaptic vesicle recycling of specific neural subsets with the Gal4/UAS system at the restrictive temperature, we specifically blocked visual and olfactory memory retrieval, either alone or in combination; memory acquisition remained intact for these modalities. Blocking the memory retrieval of the reinforced olfactory cues did not impair the conditioned response to the unreinforced visual cues or vice versa, in contrast to the canonical memory-retrieval processing of sensory preconditioning. In addition, these conditioned responses can be abolished by blocking the memory retrieval of the two modalities simultaneously. In sum, our results indicated that a conditioned response to an unreinforced cue in cross-modal sensory preconditioning can be recalled through parallel pathways.
Revisited: Haemodynamic Instability and Endocrine Response During Endotracheal Tube-Placement. A Prospective, Randomized Trial Using Topical Lidocaine and a Lightwand

Endotracheal intubation via direct laryngoscopy frequently provokes cardiovascular side-effects. Although us- ing a lightwand intubation device reduces laryngeal stimulation, previous reports indicated a similar stress response com- pared to classical laryngoscopy. We hypothesized that endotracheal tube (ET) placement itself elicits haemodynamic in- stability and that topical anaesthesia can attenuate this response. Methods: 30 patients were randomized to three groups (n = 10 each). After induction of general anaesthesia (fentanyl, etomidate, vecuronium) 5 ml of test solution was applied to laryngo-tracheal structures via a lightwand guided EDGAR- Tube ® . Control group received 5 ml saline 0.9%, group lido 1% 5 ml lidocaine 1%, and group lido 2% 5 ml lidocaine 2%. After 2 minutes of bag-mask ventilation lightwand guided ET placement was performed. Invasive systolic arterial pres- sure (SAP, mmHg), heart rate (HR, bpm) and arterial plasma concentrations of catecholamines ((adr)(nor), pcg ml-) were determined. Results: After ET placement control group patients showed increased HR and SAP (meanHR = 15.3; meanSAP = 45.6) compared to both lido groups (� HR: lido1%/2% = 5.8/3.7; � SAP: lido1%2% = 8.7/13.0). Catecholamine concen- trations also increased only in the control group (mean � (adr) = 101.43; � (nor) = 89.41) but not in lido groups (� (adr): lido1%/2% = -12.93/7.05; � (nor): lido1%/2% = -6.61/-30.55). Effect size calculation indicated strong clinical effects of topical lidocaine for almost all variables (ES > 0.8). Conclusion: ET placement into the non-anaesthesized trachea causes haemodynamic and endocrine stress even if direct laryngoscopy is omitted. Topical anaesthesia effectively reduces this response.
A step-wise genetic-algorithm-based approach for improving the sustainability of any country and for determining the characteristics of the ideally sustainable country

A step-wise genetic algorithm (GA)-based approach is put forward for (a) guiding any interested country on how to optimally improve its environmental sustainability (ES), and (b) determining the characteristics of the (theoretically) maximally sustainable country. The Environmental Sustainability Index (ESI) 2005 is used to this end, with the GA genes, chromosomes, and fitness values corresponding to the ESI 2005 indicators, sets of indicator values, and scores, respectively. Following GA operation, any interested country can increase - and, ideally, maximise - its ES via the following procedure: a chromosome with similar gene values to the ESI indicator values of the interested country, but demonstrating higher fitness (ESI score), is appropriately selected from any GA generation such that the changes that are necessary in order for the country's ESI indicator values to match those of the selected chromosome to be not only implementable, but furthermore capable of producing the maximal improvement in terms of ES. By repeating this procedure on each updated version of the interested country, the country's indicator values and ESI score are progressively modified towards maximal ES. Alternative optimisation approaches, such as pattern search (PS) and simulated annealing (SA), are also capable of reaching maximal ES, yet - due to their single-state basis of operation - do not permit the concurrent investigation of alternative paths towards maximal ES, and - furthermore - do not guarantee the identification of the appropriate indicator(s) to be modified. An interesting finding that is common to GA, PS, and SA operation is that the fitness values of the best chromosomes/states invariably exceed not only the ESI score of the top-ranking ESI 2005 country (75.1 of Finland), but - furthermore - the “perfect” ESI 2005 score of 100 by around 10, thus putting into question the construction details of the ESI 2005.1
Muscarinic cholinergic receptors modulate inhibitory synaptic rhythms in hippocampus and neocortex

Activation of muscarinic acetylcholine (ACh) receptors (mAChRs) powerfully affects many neuronal properties as well as numerous cognitive behaviors. Small neuronal circuits constitute an intermediate level of organization between neurons and behaviors, and mAChRs affect interactions among cells that compose these circuits. Circuit activity is often assessed by extracellular recordings of the local field potentials (LFPs), which are analogous to in vivo EEGs, generated by coordinated neuronal interactions. Coherent forms of physiologically relevant circuit activity manifest themselves as rhythmic oscillations in the LFPs. Frequencies of rhythmic oscillations that are most closely associated with animal behavior are in the range of 4–80 Hz, which is subdivided into theta (4–14 Hz), beta (15–29 Hz) and gamma (30–80 Hz) bands. Activation of mAChRs triggers rhythmic oscillations in these bands in the hippocampus and neocortex. Inhibitory responses mediated by GABAergic interneurons constitute a prominent feature of these oscillations, and indeed, appear to be their major underlying factor in many cases. An important issue is which interneurons are involved in rhythm generation. Besides affecting cellular and network properties directly, mAChRs can cause the mobilization of endogenous cannabinoids (endocannabinoids, eCBs) that, by acting on the principal cannabinoid receptor of the brain, CB1R, regulate the release of certain neurotransmitters, including GABA. CB1Rs are heavily expressed on only a subset of interneurons and, at lower density, on glutamatergic neurons. Exogenous cannabinoids typically disrupt oscillations in the theta (θ) and gamma (γ) ranges, which probably contributes to the behavioral effects of these drugs. It is important to understand how neuronal circuit activity is affected by mAChR-driven eCBs, as this information will provide deeper insight into the actions of ACh itself, as well as into the effects of eCBs and exogenous cannabinoids in animal behavior. After covering some basic aspects of the mAChR system, this review will focus on recent findings concerning the mechanisms and circuitry that generate θ and γ rhythms in hippocampus and neocortex. The ability of optogenetic methods to probe the many roles of ACh in rhythm generation is highlighted.
Sequence Polymorphism, Predicted Secondary Structures, and Surface-Exposed Conformational Epitopes of Campylobacter Major Outer Membrane Protein

ABSTRACT The major outer membrane protein (MOMP), a putative porin and a multifunction surface protein of Campylobacter jejuni, may play an important role in the adaptation of the organism to various host environments. To begin to dissect the biological functions and antigenic features of this protein, the gene (designatedcmp) encoding MOMP was identified and characterized from 22 strains of C. jejuni and one strain of C. coli. It was shown that the single-copy cmp locus encoded a protein with characteristics of bacterial outer membrane proteins. Prediction from deduced amino acid sequences suggested that each MOMP subunit consisted of 18 β-strands connected by short periplasmic turns and long irregular external loops. Alignment of the amino acid sequences of MOMP from different strains indicated that there were seven localized variable regions dispersed among highly conserved sequences. The variable regions were located in the putative external loop structures, while the predicted β-strands were formed by conserved sequences. The sequence homology of cmp appeared to reflect the phylogenetic proximity of C. jejuni strains, since strains with identical cmp sequences had indistinguishable or closely related macrorestriction fragment patterns. Using recombinant MOMP and antibodies recognizing linear or conformational epitopes of the protein, it was demonstrated that the surface-exposed epitopes of MOMP were predominantly conformational in nature. These findings are instrumental in the design of MOMP-based diagnostic tools and vaccines.
Long-term effects of public policy for displaced workers in Sweden: Shipyard workers in the west and miners in the north

The objective of this paper is to study the long term effects of public policy measures for displaced workers. Our focus is on the individuals affected by the cutbacks at the LKAB iron ore mines in northern Sweden in 1983 and the closure of the Uddevalla Shipyard in western Sweden in 1985. These workers not only experienced job loss, but were also the target group for extraordinary labour market policies. Using register data from Statistics Sweden (labour market status, earnings, education etc.), we follow those affected until 1999. We compare this with the corresponding development of a large sample other workers who lost their jobs because of plant closures in 1987–88 but who did not receive extraordinary measures. Estimations of the net effect of the extraordinary measures find that they did have positive long-term effects for the displaced shipyard workers and miners. They have higher employment, not higher unemployment, and higher earnings than the comparison group.
Transboundary pollution, R&D spillovers, absorptive capacity and international trade

In this paper, we study the effects of absorptive capacity and R&D spillovers on cross -border pollution in a game played by two regulator-firm hierarchies. By means of a tax per-unit of pollution, a subsidy per- unit of original research and a subsidy per-unit of absorptive research, the regulators can reach the first -best outcome. We show that, in addition to free R&D spillovers and absorptive research, competition of firms on the common market help non -cooperating countries to better internalize transboundary pollution. More importantly, opening borders increase the per -unitemission- tax and decrease the per-unit original research subsidy. Thus, when the investment-costparameters are sufficiently high, the international trade increases the original research, production.Consequently, the emission ratio is lower.
In vitro Antiproliferative and Antibacterial Activities of Essential Oils from Four Species of Guatteria

The essential oils (EOs) extracted from four species of the genus Guatteria, G. australis, G. ferruginea, G. latifolia, and G. sellowiana were analyzed. A total of 24, 22, 25, and 19 constituents of the oils from four species, respectively, were identified by GC/MS. These oils showed qualitative and quantitative differences. All the oils contained the oxygenated sesquiterpenes spathulenol (11.04 – 40.29%) and caryophyllene oxide (7.74 – 40.13%) as predominant constituents. Evaluation of antiproliferative activity of the EOs showed strong selectivity (1.1 – 4.1 μg/ml) against the tumor cell line OVCAR‐03 (ovarian cancer), i.e., more active than the positive control doxorubicin (11.7 μg/ml). All EOs showed strong antibacterial activity (minimum inhibitory concentrations of 0.062 – 0.25 mg/ml) against strains of Rhodococcus equi.
Selection on outlier loci and their association with adaptive phenotypes in Littorina saxatilis contact zones

A fundamental issue in speciation research is to evaluate phenotypic variation and the genomics driving the evolution of reproductive isolation between sister taxa. Above all, hybrid zones are excellent study systems for researchers to examine the association of genetic differentiation, phenotypic variation and the strength of selection. We investigated two contact zones in the marine gastropod Littorina saxatilis and utilized landmark‐based geometric morphometric analysis together with amplified fragment length polymorphism (AFLP) markers to assess phenotypic and genomic divergence between ecotypes under divergent selection. From genetic markers, we calculated the cline width, linkage disequilibrium and the average effective selection on a locus. Additionally, we conducted an association analysis linking the outlier loci and phenotypic variation between ecotypes and show that a proportion of outlier loci are associated with key adaptive phenotypic traits.
Including Students with Moderate and Severe Disabilities in Extracurricular and Community Recreation Activities

vital role in all our lives, and educators have long recognized that such activities are an important instructional emphasis for students with moderate and severe disabilities (Bambara, Browder, & Koger, 2006; Browder & Cooper, 2001; Rynders & Schleien, 1993). This article offers teachers practical strategies for including their students with disabilities in school extracurricular activities, as well as in community recreation activities. Since the passage of the Individuals With Disabilities Education Improvement Act (IDEA, 2004) and the No Child Left Behind Act of 2001 (NCLB, 2001), educators have increasingly recognized the general curriculum—or core academic content—as an instructional focus for all students, including students with moderate and severe intellectual disabilities. However, the importance of this new focus does not mean that parents and educators should neglect students’ other instructional needs. Recreation, leisure, and extracurricular involvement are essential for developing friendships, increasing the likelihood of community integration and postschool success, and improving the overall quality of life (Heward, 2006; Modell & Valdez, 2002). Moreover, extracurricular involvement—through such activities as participating in science programs, using computers, practicing foreign languages, working on yearbooks, and participating in 4-H clubs can also give students with moderate and severe disabilities many opportunities to practice and extend their academic skills. Students with significant intellectual disabilities need meaningful opportunities and explicit instruction so that they can develop the critical skills they need for participating in school and community recreation activities (Bambara et al., 2006; Collins, Hall, & Branson, 1997; Modell & Valdez, 2002). Without