Miracle-dz/UniFAR-FTUs huggingface dataset:
DNA Synthesis by Primer Exchange Reaction Cascades

Swap and extend: The autonomous synthesis of single-stranded DNA molecules of arbitrary size and sequence composition can easily be achieved by primer exchange reaction (PER) cascades, in which the sequential polymerase-mediated extension of DNA primers is guided by catalytic hairpins. This highlight illustrates the potential of this method for applications in DNA nanotechnology.
Modeling complexes of modeled proteins

Structural characterization of proteins is essential for understanding life processes at the molecular level. However, only a fraction of known proteins have experimentally determined structures. This fraction is even smaller for protein–protein complexes. Thus, structural modeling of protein–protein interactions (docking) primarily has to rely on modeled structures of the individual proteins, which typically are less accurate than the experimentally determined ones. Such “double” modeling is the Grand Challenge of structural reconstruction of the interactome. Yet it remains so far largely untested in a systematic way. We present a comprehensive validation of template‐based and free docking on a set of 165 complexes, where each protein model has six levels of structural accuracy, from 1 to 6 Å Cα RMSD. Many template‐based docking predictions fall into acceptable quality category, according to the CAPRI criteria, even for highly inaccurate proteins (5–6 Å RMSD), although the number of such models (and, consequently, the docking success rate) drops significantly for models with RMSD > 4 Å. The results show that the existing docking methodologies can be successfully applied to protein models with a broad range of structural accuracy, and the template‐based docking is much less sensitive to inaccuracies of protein models than the free docking. Proteins 2017; 85:470–478. © 2016 Wiley Periodicals, Inc.
Standard echocardiography versus handheld echocardiography for the detection of subclinical rheumatic heart disease: protocol for a systematic review

Introduction Rheumatic heart disease (RHD) is a preventable and treatable chronic condition which persists in many developing countries largely affecting impoverished populations. Handheld echocardiography presents an opportunity to address the need for more cost-effective methods of diagnosing RHD in developing countries, where the disease continues to carry high rates of morbidity and mortality. Preliminary studies have demonstrated moderate sensitivity as well as high specificity and diagnostic odds for detecting RHD in asymptomatic patients. We describe a protocol for a systematic review on the diagnostic performance of handheld echocardiography compared to standard echocardiography using the 2012 World Heart Federation criteria for diagnosing subclinical RHD. Methods and analysis Electronic databases including PubMed, Scopus, Web of Science and EBSCOhost as well as reference lists and citations of relevant articles will be searched from 2012 to date using a predefined strategy incorporating a combination of Medical Subject Heading terms and keywords. The methodological validity and quality of studies deemed eligible for inclusion will be assessed against review specific Quality Assessment of Diagnostic Accuracy Studies 2 criteria and information on metrics of diagnostic accuracy and demographics extracted. Forest plots of sensitivity and specificity as well as scatter plots in receiver operating characteristic (ROC) space will be used to investigate heterogeneity. If possible, a meta-analysis will be conducted to produce summary results of sensitivity and specificity using the Hierarchical Summary ROC method. In addition, a sensitivity analysis will be conducted to investigate the effect of studies with a high risk of bias. Ethics and dissemination Ethics approval is not required for this systematic review of previously published literature. The planned review will provide a summary of the diagnostic accuracy of handheld echocardiography. Results may feed into evidence-based guidelines and should the findings of this review warrant a change in clinical practice, a summary report will be disseminated among leading clinicians and healthcare professionals in the field. PROSPERO registration number CRD42016051261.
Bioturbation and directionality in Earth's carbon isotope record across the Neoproterozoic–Cambrian transition

Mixing of sediments by moving animals becomes apparent in the trace fossil record from about 550 million years ago (Ma), loosely overlapping with the tail end of the extreme carbonate carbon isotope δ13Ccarbonate fluctuations that qualitatively distinguish the Proterozoic geochemical record from that of the Phanerozoic. These Precambrian‐scale fluctuations in δ13Ccarbonate (PSF‐δ13Ccarbonate) remain enigmatic, due to their high amplitude and inclusion of global‐scale negative δ13Ccarbonate values, below anything attributable to mantle input. Here, we note that different biogeochemical‐model scenarios plausibly explaining globally synchronous PSF‐δ13Ccarbonate converge: via mechanistic requirements for extensive anoxia in marine sediments to support sedimentary build‐up of 13C‐depleted carbon. We hypothesize that bioturbation qualitatively reduced marine sediment anoxia by exposing sediments to oxygenated overlying waters, which ultimately contributed to decreasing the carbon cycle's subsequent susceptibility to PSF‐ δ13Ccarbonate. Bioturbation may also have reduced the quantity of (isotopically light) organic‐derived carbon available to contribute to PSF‐ δ13Ccarbonate via ocean crust carbonatization at depth. We conduct a comparative modelling exercise in which we introduce bioturbation to existing model scenarios for PSF‐ δ13Ccarbonate: expressing both the anoxic proportion of marine sediments, and the global organic carbon burial efficiency, as a decreasing function of bioturbation. We find that bioturbation's oxygenating impact on sediments has the capacity to prevent PSF‐ δ13Ccarbonate caused by authigenic carbonate precipitation or methanogenesis. Bioturbation's impact on the f‐ratio via remineralization is partially offset by liberation of organic phosphate, some of which feeds back into new production. We emphasize that this study is semiquantitative, exploratory and intended merely to provide a qualitative theoretical framework within which bioturbation's impact on long‐term, first‐order δ13Ccarbonate can be assessed (and it is hoped quantified in more detail by future work). With this proviso, we conclude that it is entirely plausible that bioturbation made a decisive contribution to the enigmatic directionality in the δ13Ccarbonate record, from the Neoproterozoic–Cambrian boundary onwards.
Mixture model-based association analysis with case-control data in genome wide association studies

Abstract Multilocus haplotype analysis of candidate variants with genome wide association studies (GWAS) data may provide evidence of association with disease, even when the individual loci themselves do not. Unfortunately, when a large number of candidate variants are investigated, identifying risk haplotypes can be very difficult. To meet the challenge, a number of approaches have been put forward in recent years. However, most of them are not directly linked to the disease-penetrances of haplotypes and thus may not be efficient. To fill this gap, we propose a mixture model-based approach for detecting risk haplotypes. Under the mixture model, haplotypes are clustered directly according to their estimated disease penetrances. A theoretical justification of the above model is provided. Furthermore, we introduce a hypothesis test for haplotype inheritance patterns which underpin this model. The performance of the proposed approach is evaluated by simulations and real data analysis. The results show that the proposed approach outperforms an existing multiple testing method.
Applying an MDA-Based Approach to Consider Security Rules in the Development of Secure DWs

Data Warehouses (DWs) manage crucial information for enterprises which must be protected from unauthorized accesses. The question of which security issues are present in all stages of the DW design is therefore of great importance when considering these security constraints in design decisions. We have used the Model Driven Architecture (MDA) approach to propose an MDA architecture with which to develop secure DWs, which defines secure models at different abstraction levels along with their automatic transformation between models. Our approach considers a multidimensional path towards On-Line Analytical Processing (OLAP) tools, but did not, until now, support the transformation of complex security rules from conceptual models. After carrying out a modification of our conceptual metamodel to support a better representation of security rules and to define several sets of transformation rules, this paper shows how to transform these security rules through an example.
Next-Generation Sequence Analysis Reveals Transfer of Methicillin Resistance to a Methicillin-Susceptible Staphylococcus aureus Strain That Subsequently Caused a Methicillin-Resistant Staphylococcus aureus Outbreak: a Descriptive Study

ABSTRACT Resistance to methicillin in Staphylococcus aureus is caused primarily by the mecA gene, which is carried on a mobile genetic element, the staphylococcal cassette chromosome mec (SCCmec). Horizontal transfer of this element is supposed to be an important factor in the emergence of new clones of methicillin-resistant Staphylococcus aureus (MRSA) but has been rarely observed in real time. In 2012, an outbreak occurred involving a health care worker (HCW) and three patients, all carrying a fusidic acid-resistant MRSA strain. The husband of the HCW was screened for MRSA carriage, but only a methicillin-susceptible S. aureus (MSSA) strain, which was also resistant to fusidic acid, was detected. Multiple-locus variable-number tandem-repeat analysis (MLVA) typing showed that both the MSSA and MRSA isolates were MT4053-MC0005. This finding led to the hypothesis that the MSSA strain acquired the SCCmec and subsequently caused an outbreak. To support this hypothesis, next-generation sequencing of the MSSA and MRSA isolates was performed. This study showed that the MSSA isolate clustered closely with the outbreak isolates based on whole-genome multilocus sequence typing and single-nucleotide polymorphism (SNP) analysis, with a genetic distance of 17 genes and 44 SNPs, respectively. Remarkably, there were relatively large differences in the mobile genetic elements in strains within and between individuals. The limited genetic distance between the MSSA and MRSA isolates in combination with a clear epidemiologic link supports the hypothesis that the MSSA isolate acquired a SCCmec and that the resulting MRSA strain caused an outbreak.
Age Differences in False Memory: The Importance of Retrieval Monitoring Processes and Their Modulation by Memory Quality

Older adults are more likely than younger adults to falsely recall past episodes that occurred differently or not at all. We examined whether older adults’ propensity for false associative memory is related to declines in postretrieval monitoring processes and their modulation with varying memory representations. Younger (N = 20) and older adults (N = 32) studied and relearned unrelated scene-word pairs, followed by a final cued recall that was used to distribute the pairs for an associative recognition test 24 hours later. This procedure allowed individualized formation of rearranged pairs that were made up of elements of pairs that were correctly recalled in the final cued recall (“high-quality” pairs), and of pairs that were not correctly recalled (“low-quality” pairs). Both age groups falsely recognized more low-quality than high-quality rearranged pairs, with a less pronounced reduction in false alarms to high-quality pairs in older adults. In younger adults, cingulo-opercular activity was enhanced for false alarms and for low-quality correct rejections, consistent with its role in postretrieval monitoring. Older adults did not show such modulated recruitment, suggesting deficits in their selective engagement of monitoring processes given variability in the fidelity of memory representations. There were no age differences in hippocampal activity, which was higher for high-quality than low-quality correct rejections in both age groups. These results demonstrate that the engagement of cingulo-opercular monitoring mechanisms varies with memory representation quality and contributes to age-related deficits in false associative memory.
Analysis of mtDNA/nDNA Ratio in Mice

Mitochondrial DNA (mtDNA) lacks the protection provided by the nucleosomes in the nuclear DNA and does not have a DNA repair mechanism, making it highly susceptible to damage, which can lead to mtDNA depletion. mtDNA depletion compromises the efficient function of cells and tissues and thus impacts negatively on health. Here, we describe a brief and easy protocol to quantify mtDNA copy number by determining the mtDNA/nDNA ratio. The procedure has been validated using a cohort of young and aged mice. © 2017 by John Wiley & Sons, Inc.
Pressure ulcer risk detection from complexity of activity

Activity levels in nursing home residents were measured with accelerometers over one week as part of a multicenter randomized controlled trial, and complexity of the resulting activity patterns were characterized. Among 813 study participants on whom activity data had been collected, 16 participants developed pressure ulcers by the end of the study. The fractal dimension D0 of the activity series was lower (p=0.039) in residents who developed pressure ulcers than in controls matched on the basis of race, randomization group, score on the Braden scale, and diagnoses of cardiovascular disease and dementia. Hurst exponents indicated that the scaling of the power spectrum was close to 1/ƒ in pressure ulcer cases. At timescales exceeding 30 minutes, approximate entropy tended to be higher in the controls than in the pressure ulcer cases. The fractal structure of the activity time series and its information content offer the ability to predict higher risk of development of pressure ulcers in nursing home residents.
The Probit Choice Model under Sequential Search with an Application to Online Retailing

We develop a probit choice model under optimal sequential search and apply it to the study of aggregate demand of consumer durable goods. In our joint model of search and choice, we derive a semi-closed form expression for the probability of choice that obeys the full set of restrictions imposed by optimal sequential search. Our joint model leads to a partial simulation-based estimation that avoids high-dimensional integrations in the evaluation of choice probabilities and that is particularly attractive when search sets are large. We illustrate the advantages of our approach using aggregate search and choice data from the camcorder product category at Amazon.com. We show that the joint use of search and choice data provides better performance in terms of inferences and predictions than using search data alone and leads to realistic estimates of consumer substitution patterns.
An in vitro assay for prediction of broiler intestinal viscosity and growth when fed rye-based diets in the presence of exogenous enzymes.

A two-stage in vitro assay procedure was developed for predicting the efficacy of microbial enzyme sources in rye-based diets for broiler chicks. The procedure uses the complete diet as substrate to predict the in vivo intestinal viscosity and final weight of birds fed such diets. The optimum conditions for maximizing in vitro viscosity of a rye-based diet consisted of digesting . 6 g of diet (ground through a 1-mm screen) in . 9 mL of . 1 N HCl containing 2,000 U pepsin/mL for 45 min at 40 C. At the end of this incubation phase, . 3 mL 1 M NaHCO3 containing 8 mg pancreatin/mL (8 x USP) was added and the tube sealed and incubated for 2 h with intermittent vortexing. The digesta was then centrifuged (12,700 x g) and the supernatant collected for viscosity analysis using a digital viscometer. This assay was used for a rye-based diet containing either 0, . 1, . 2, . 4, . 8, or 1.6% of a xylanase source (experimental Trichoderma longibrachiatum product). The results were compared to weight and intestinal viscosity proximal and distal to Meckel's diverticulum of broilers (19 days of age) that had been fed these diets. The in vitro assay accurately predicted the in vivo intestinal viscosity (proximal r2 = .758, P < .0001, distal r2 = .667, P < .0001) and final weight of these birds (r2 = .660, P < .0001). The data suggest that the in vitro assay is a reliable assay for assessing the growth-promoting ability of an enzyme preparation in chicks fed rye-based diets.
Cortical Connections Position Primate Area 25 as a Keystone for Interoception, Emotion, and Memory

The structural and functional integrity of subgenual cingulate area 25 (A25) is crucial for emotional expression and equilibrium. A25 has a key role in affective networks, and its disruption has been linked to mood disorders, but its cortical connections have yet to be systematically or fully studied. Using neural tracers in rhesus monkeys, we found that A25 was densely connected with other ventromedial and posterior orbitofrontal areas associated with emotions and homeostasis. A moderate pathway linked A25 with frontopolar area 10, an area associated with complex cognition, which may regulate emotions and dampen negative affect. Beyond the frontal lobe, A25 was connected with auditory association areas and memory-related medial temporal cortices, and with the interoceptive-related anterior insula. A25 mostly targeted the superficial cortical layers of other areas, where broadly dispersed terminations comingled with modulatory inhibitory or disinhibitory microsystems, suggesting a dominant excitatory effect. The architecture and connections suggest that A25 is the consummate feedback system in the PFC. Conversely, in the entorhinal cortex, A25 pathways terminated in the middle-deep layers amid a strong local inhibitory microenvironment, suggesting gating of hippocampal output to other cortices and memory storage. The graded cortical architecture and associated laminar patterns of connections suggest how areas, layers, and functionally distinct classes of inhibitory neurons can be recruited dynamically to meet task demands. The complement of cortical connections of A25 with areas associated with memory, emotion, and somatic homeostasis provide the circuit basis to understand its vulnerability in psychiatric and neurologic disorders. SIGNIFICANCE STATEMENT Integrity of the prefrontal subgenual cingulate cortex is crucial for healthy emotional function. Subgenual area 25 (A25) is mostly linked with other prefrontal areas associated with emotion in a dense network positioned to recruit large fields of cortex. In healthy states, A25 is associated with internal states, autonomic function, and transient negative affect. Constant hyperactivity in A25 is a biomarker for depression in humans and may trigger extensive activation in its dominant connections with areas associated with emotions and internal balance. A pathway between A25 and frontopolar area 10 may provide a critical link to regulate emotions and dampen persistent negative affect, which may be explored for therapeutic intervention in depression.
wtf genes are prolific dual poison-antidote meiotic drivers

Meiotic drivers are selfish genes that bias their transmission into gametes, defying Mendelian inheritance. Despite the significant impact of these genomic parasites on evolution and infertility, few meiotic drive loci have been identified or mechanistically characterized. Here, we demonstrate a complex landscape of meiotic drive genes on chromosome 3 of the fission yeasts Schizosaccharomyces kambucha and S. pombe. We identify S. kambucha wtf4 as one of these genes that acts to kill gametes (known as spores in yeast) that do not inherit the gene from heterozygotes. wtf4 utilizes dual, overlapping transcripts to encode both a gamete-killing poison and an antidote to the poison. To enact drive, all gametes are poisoned, whereas only those that inherit wtf4 are rescued by the antidote. Our work suggests that the wtf multigene family proliferated due to meiotic drive and highlights the power of selfish genes to shape genomes, even while imposing tremendous costs to fertility. DOI: http://dx.doi. org/10.7554/eLife.26033. 001
The Helping Hand: An Assistive Manipulation Framework Using Augmented Reality and a Tongue-Drive

A human-in-the-loop system is proposed to enable collaborative manipulation tasks for person with physical disabilities. Studies have shown the cognitive burden of subject is reduced with increased autonomy of assistive system. Our framework is aim to communicate high-level intent from subject and generate desired manipulations. We elaborate a framework by incorporating a tongue-drive system and a 7 DoF robotic arm through an virtual interface. The assistive system processes sensor input for interpreting users environment, and the subject provides an ego-centric visual feedback via interface to guide action loop for achieving the tasks. Extensive experiments are performed on our framework and we show our coupled feedback loops is able to effectively simplify complex manipulation tasks.
The Potential for Synovium-derived Stem Cells in Cartilage Repair.

BACKGROUND Articular cartilage defects often result in pain, loss of function and finally osteoarthritis. Developing cell-based therapies for cartilage repair is a major goal of orthopaedic research. Autologous chondrocyte implantation is currently the gold standard cell-based surgical procedure for the treatment of large, isolated, full thickness cartilage defects. Several disadvantages such as the need for two surgical procedures or hypertrophic regenerative cartilage, underline the need for alternative cell sources. OBJECTIVE Mesenchymal stem cells, particularly synovium-derived mesenchymal stem cells, represent a promising cell source. Synovium-derived mesenchymal stem cells have attracted considerable attention since they display great chondrogenic potential and less hypertrophic differentiation than mesenchymal stem cells derived from bone marrow. The aim of this review was to summarize the current knowledge on the chondrogenic potential for synovial stem cells in regard to cartilage repair purposes. RESULTS A literature search was carried out identifying 260 articles in the databases up to January 2017. Several in vitro and initial animal in vivo studies of cartilage repair using synovia stem cell application showed encouraging results. Since synvoium-derived stem cells are located in the direct vicinity of cartilage and cartilage lesions these cells might even contribute to natural cartilage regeneration. The only one published human in vivo study with 10 patients revealed good results concerning postoperative outcome, MRI, and histologic features after a two-stage implantation of synovial stem cells into an isolated cartilage defect of the femoral condyle. CONCLUSION Synovium-derived stem cells possess great chondrogenic potential and showed encouraging results for cartilage repair purposes. Furthermore, synovial stem cells play an important role in joint homeostasis and possibly in natural cartilage repair. Further studies are needed to elucidate the interplay of synovial stem cells and chondrocytes, and the promising role of synovium-derived stem cells in cartilage tissue engineering.