Miracle-dz/UniFAR-FTUs huggingface dataset:
Antibody-dependent enhancement of severe dengue disease in humans

Too much or too little—better than some Dengue fever is caused by a mosquito-transmitted flavivirus resembling Zika virus. Both viruses can cause severe diseases in humans with catastrophic sequelae. It has been suspected in humans, and shown in animal models, that the host's immune responses can make disease worse. Katzelnick et al. examined data from a long-term study of Nicaraguan children exposed to dengue virus (see the Perspective by Feinberg and Ahmed). They confirmed that antibody-dependent enhancement of disease occurs at a specific range of antibody concentrations. Low levels of antibody did not enhance disease, intermediate levels exacerbated disease, and high antibody titers protected against severe disease. These findings have major implications for vaccines against flaviviruses. Indeed, recent vaccine trials have shown evidence of severe disease in some recipients who were previously exposed to virus. Science, this issue p. 929; see also p. 865 A long-term Nicaraguan pediatric cohort reveals that a narrow range of preexisting antibody titers increases the risk of severe dengue disease. For dengue viruses 1 to 4 (DENV1-4), a specific range of antibody titer has been shown to enhance viral replication in vitro and severe disease in animal models. Although suspected, such antibody-dependent enhancement of severe disease has not been shown to occur in humans. Using multiple statistical approaches to study a long-term pediatric cohort in Nicaragua, we show that risk of severe dengue disease is highest within a narrow range of preexisting anti-DENV antibody titers. By contrast, we observe protection from all symptomatic dengue disease at high antibody titers. Thus, immune correlates of severe dengue must be evaluated separately from correlates of protection against symptomatic disease. These results have implications for studies of dengue pathogenesis and for vaccine development, because enhancement, not just lack of protection, is of concern.
FFRob: Leveraging symbolic planning for efficient task and motion planning

Mobile manipulation problems involving many objects are challenging to solve due to the high dimensionality and multi-modality of their hybrid configuration spaces. Planners that perform a purely geometric search are prohibitively slow for solving these problems because they are unable to factor the configuration space. Symbolic task planners can efficiently construct plans involving many variables but cannot represent the geometric and kinematic constraints required in manipulation. We present the FFRob algorithm for solving task and motion planning problems. First, we introduce extended action specification (EAS) as a general purpose planning representation that supports arbitrary predicates as conditions. We adapt existing heuristic search ideas for solving strips planning problems, particularly delete-relaxations, to solve EAS problem instances. We then apply the EAS representation and planners to manipulation problems resulting in FFRob. FFRob iteratively discretizes task and motion planning problems using batch sampling of manipulation primitives and a multi-query roadmap structure that can be conditionalized to evaluate reachability under different placements of movable objects. This structure enables the EAS planner to efficiently compute heuristics that incorporate geometric and kinematic planning constraints to give a tight estimate of the distance to the goal. Additionally, we show FFRob is probabilistically complete and has a finite expected runtime. Finally, we empirically demonstrate FFRob’s effectiveness on complex and diverse task and motion planning tasks including rearrangement planning and navigation among movable objects.
Delaying Chemotherapy in the Treatment of Stage IV Non-Small Cell Lung Cancer Does Not Adversely Affect Survival Outcome

Background: Whether a delay in the initiation of chemotherapy for advanced non-small cell lung cancer (NSCLC) can affect overall survival is not well studied. We aim to evaluate the effect of the time interval between diagnosis and initiation of chemotherapy on overall survival in patients with stage IV NSCLC. Methods: A retrospective review of newly diagnosed stage IV NSCLC patients who received chemotherapy between 1995 and 2012 was conducted. Demographics, histology and site(s) of metastases of patients were reviewed. Time interval between the date of diagnosis and the date of starting chemotherapy was calculated in days. Patients were divided in two groups based on median time interval: Group A 46 days. The primary end point was the difference in overall survival between the two groups. Results: A total of 172 patients were reviewed. Each group had 86 patients. Median age for both groups was 61 years. The most common histology was adenocarcinoma in A and B (43% vs. 45%, respectively). The sites of metastases in A and B were: brain (25% vs. 28%), liver (20% vs. 9%), bone (30% vs. 30%), respectively. Performance status of ECOG (Eastern Cooperative Oncology Group) :( 0-1) was 82% vs. 76% in A and B, respectively. The median overall survival for A was 7 months vs.12 months for B (p=0.04). Conclusion: In this single institution review, delayed chemotherapy for stage IV NSCLC more than 46 days did not have a detrimental effect on overall survival and even suggested a better outcome. Further larger and prospective studies are warranted to validate these findings.
Application of dGNSS in Alpine Ski Racing: Basis for Evaluating Physical Demands and Safety

External forces, such as ground reaction force or air drag acting on athletes' bodies in sports, determine the sport-specific demands on athletes' physical fitness. In order to establish appropriate physical conditioning regimes, which adequately prepare athletes for the loads and physical demands occurring in their sports and help reduce the risk of injury, sport-and/or discipline-specific knowledge of the external forces is needed. However, due to methodological shortcomings in biomechanical research, data comprehensively describing the external forces that occur in alpine super-G (SG) and downhill (DH) are so far lacking. Therefore, this study applied new and accurate wearable sensor-based technology to determine the external forces acting on skiers during World Cup (WC) alpine skiing competitions in the disciplines of SG and DH and to compare these with those occurring in giant slalom (GS), for which previous research knowledge exists. External forces were determined using WC forerunners carrying a differential global navigation satellite system (dGNSS). Combining the dGNSS data with a digital terrain model of the snow surface and an air drag model, the magnitudes of ground reaction forces were computed. It was found that the applied methodology may not only be used to track physical demands and loads on athletes, but also to simultaneously investigate safety aspects, such as the effectiveness of speed control through increased air drag and ski–snow friction forces in the respective disciplines. Therefore, the component of the ground reaction force in the direction of travel (ski–snow friction) and air drag force were computed. This study showed that (1) the validity of high-end dGNSS systems allows meaningful investigations such as characterization of physical demands and effectiveness of safety measures in highly dynamic sports; (2) physical demands were substantially different between GS, SG, and DH; and (3) safety-related reduction of skiing speed might be most effectively achieved by increasing the ski–snow friction force in GS and SG. For DH an increase in the ski–snow friction force might be equally as effective as an increase in air drag force.
Living environment and its relationship to depressive mood: A systematic review

Background and aims: The notion that environment affects mental health has a long history; in this systematic review, we aimed to study whether the living environment is related to depressive mood. Methods: We searched databases of PubMed, Scopus and Web of Science for population-based original studies prior to October 2016. We included studies that measured depressive symptoms or depression and had measures of urbanization, population density, aesthetics of living environment, house/built environment, green areas, walkability, noise, air pollution or services. Results: Out of 1,578 articles found, 44 studies met our inclusion criteria. Manual searches of the references yielded 13 articles, resulting in 57 articles being included in the systematic review. Most of the studies showed statistically significant associations with at least one of the characteristics of living environment and depressive mood. House and built environment with, for example, poor housing quality and non-functioning, lack of green areas, noise and air pollution were more clearly related to depressive mood even after adjustment for different individual characteristics. On the contrary, the results in relation to population density, aesthetics and walkability of living environment, and availability of services and depressive mood were more inconsistent. Conclusion: Adverse house/built environment, including poor housing quality and non-functioning, lack of green spaces, noise and air pollution are related to depressive mood and should be taken into account during planning in order to prevent depressive mood.
Qualification of Food Intake by the Roma Population in the Region of South Bohemia

The article presents the results of a correlation study, aimed at quantifying the food intake of the Roma population in the South Bohemian Region. To achieve the goal, we applied the method of one-day dietary recall and frequency food analysis (non-standardized). The quantification was carried out by analysis in the Nutridan program. The study involved 302 Roma persons and 298 persons in the control group. Both groups had the same representation of males and females (50:50). The age categories of both sets differed; the average age of the Roma was lower (39.2 years) (p < 0.001). The probands from the Roma population were chosen with the help of the snowball method through known respondents. The statistical analysis shows differences in nutritional estimate between the Roma population and the control sample. The Roma differ in their energy intake. Both groups showed lower intake of sugars, below 50% total energy intake (TEI) and higher intake of fats, above 30% TEI. The respondents from both groups consume little fruits and vegetables, which may be connected with their low dietary fiber intake. In addition to the differences in the nutritional estimates, we recorded statistically significant differences in body mass index (BMI; p < 0.001), in age (p < 0.001), regular alimentation (p = 0) and demanding physical activities (p = 0). In spite of the fact our groups differed in age (the Roma are younger), it can be assumed that the obesity of the Roma may be caused by unbalanced alimentation and lack of physical activities.
Using Cranial Electrotherapy Stimulation Therapy to Treat Behavioral Health Symptoms in a Combat Operational Setting.

INTRODUCTION Addressing combat operational stress reactions (COSR) in the deployed setting can be a challenging endeavor. During the Global War on Terror, the modalities of psychotherapy and general medicine are not always feasible to manage COSR. Available behavioral health resources and practitioners remain taxed despite the most robust behavioral health billeting in recent history. Studies have suggested that COSR symptoms including sleep problems, anxiety, and depression are common presenting issues in the operational setting. Cranial electrotherapy stimulation (CES) is a treatment modality that passes low-frequency microcurrent into neuronal tissue. A growing body of research suggests that CES offers relief from symptoms associated with COSR in similar populations. A recent survey revealed that 50 to 66% of respondents using CES reported symptom improvement, with less than 1% reporting side effects. CES provided our behavioral health team with an innovative and efficient tool in improving functioning in our warfighters affected by COSR.
Cost-Aware Renewable Energy Management With Application in Cellular Networks

In this paper, we propose a cost minimization strategy for facilities with shared access to a renewable energy farm. We assume space-time varying electricity prices, and model the facilities as non-deferrable time-varying loads. A practical application of such an arrangement can be found in cellular networks, where operators can deploy a centralized energy farm to (partially) power their base stations in a given geographical area. Unlike existing works, we take into account the non-linear behavior of the battery at the energy farm, and obtain closed-form results by solving the corresponding optimization problem in continuous time. We also derive a closed-form expression which estimates the maximum cost saving in terms of the total energy harvested across the entire planning horizon. The results presented in this paper can be used to devise and benchmark low-complexity online strategies, and to understand the relationship between the maximum cost saving, the optimal consumption rate of renewable energy, and system parameters such as battery efficiency and nominal output power.
Shedding new light on RhoA signalling as a drug target in vivo using a novel RhoA-FRET biosensor mouse

ABSTRACT The small GTPase RhoA is a master regulator of signalling in cell-extracellular matrix interactions. RhoA signalling is critical to many cellular processes including migration, mechanotransduction, and is often disrupted in carcinogenesis. Investigating RhoA activity in a native tissue environment is challenging using conventional biochemical methods; we therefore developed a RhoA-FRET biosensor mouse, employing the adaptable nature of intravital imaging to a variety of settings. Mechanotransduction was explored in the context of osteocyte processes embedded in the calvaria responding in a directional manner to compression stress. Further, the migration of neutrophils was examined during in vivo “chemotaxis” in wound response. RhoA activity was tightly regulated during tissue remodelling in mammary gestation, as well as during mammary and pancreatic carcinogenesis. Finally, pharmacological inhibition of RhoA was temporally resolved by the use of optical imaging windows in fully developed pancreatic and mammary tumours in vivo. The RhoA-FRET mouse therefore constitutes a powerful tool to facilitate development of new inhibitors targeting the RhoA signalling axis.
Towards online anomaly detection by combining multiple detection methods and Storm

In this paper, we illustrate the significance and advantage of combining the results of multiple detection methods. We implement these methods as bolts in a Apache Storm cluster which is a famous real-time computation framework. We simulate two kinds of anomalies - one involving large number of small network flows and the other involving small number of large network flows. The experiments show that combining multiple methods outperforms any single detection method from the point of view of statistics. Besides, we observe that all the results are outputted in real time without delay, which means that our detection platform is indeed an effective online system.
Identification and Functional Characterization of a Novel Monotreme- Specific Antibacterial Protein Expressed during Lactation

Monotremes are the only oviparous mammals and exhibit a fascinating combination of reptilian and mammalian characters. They represent a component of synapsidal reproduction by laying shelled eggs which are incubated outside the mother’s body. This is accompanied by a prototherian lactation process, marking them as representatives of early mammals. The only extant monotremes are the platypus, and the short- and long- beaked echidnas, and their distributions are limited to Australia and New Guinea. Apart for a short weaning period, milk is the sole source of nutrition and protection for the hatchlings which are altricial and immunologically naive. The duration of lactation in these mammals is prolonged relative to the gestational length and period of incubation of eggs. Much of the development of monotreme young occurs in the non-sterile ex-utero environment. Therefore the role of milk in the growth, development and disease protection of the young is of significant interest. By sequencing the cDNA of cells harvested from monotreme milk, we have identified a novel monotreme- specific transcript, and the corresponding gene was designated as the EchAMP. The expression profile of this gene in various tissues revealed that it is highly expressed in milk cells. The peptides corresponding to the EchAMP protein have been identified in a sample of echidna milk In silico analysis indicated putative antimicrobial potential for the cognate protein of EchAMP. This was further confirmed by in vitro assays using a host of bacteria. Interestingly, EchAMP did not display any activity against a commensal gut floral species. These results support the hypothesis of enhancement of survival of the young by antimicrobial bioactives of mammary gland origin and thus emphasize the protective, non- nutritional role of milk in mammals.
Functional Neural Correlates of Attentional Deficits in Amnestic Mild Cognitive Impairment

Although amnestic mild cognitive impairment (aMCI; often considered a prodromal phase of Alzheimer’s disease, AD) is most recognized by its implications for decline in memory function, research suggests that deficits in attention are present early in aMCI and may be predictive of progression to AD. The present study used functional magnetic resonance imaging to examine differences in the brain during the attention network test between 8 individuals with aMCI and 8 neurologically healthy, demographically matched controls. While there were no significant behavioral differences between groups for the alerting and orienting functions, patients with aMCI showed more activity in neural regions typically associated with the networks subserving these functions (e.g., temporoparietal junction and posterior parietal regions, respectively). More importantly, there were both behavioral (i.e., greater conflict effect) and corresponding neural deficits in executive control (e.g., less activation in the prefrontal and anterior cingulate cortices). Although based on a small number of patients, our findings suggest that deficits of attention, especially the executive control of attention, may significantly contribute to the behavioral and cognitive deficits of aMCI.
The fission yeast nucleoporin Alm1 is required for proteasomal degradation of kinetochore components

Kinetochores (KTs) are large multiprotein complexes that constitute the interface between centromeric chromatin and the mitotic spindle during chromosome segregation. In spite of their essential role, little is known about how centromeres and KTs are assembled and how their precise stoichiometry is regulated. In this study, we show that the nuclear pore basket component Alm1 is required to maintain both the proteasome and its anchor, Cut8, at the nuclear envelope, which in turn regulates proteostasis of certain inner KT components. Consistently, alm1-deleted cells show increased levels of KT proteins, including CENP-CCnp3, spindle assembly checkpoint activation, and chromosome segregation defects. Our data demonstrate a novel function of the nucleoporin Alm1 in proteasome localization required for KT homeostasis.
Naturally Occurring Canine Melanoma as a Predictive Comparative Oncology Model for Human Mucosal and Other Triple Wild-Type Melanomas

Melanoma remains mostly an untreatable fatal disease despite advances in decoding cancer genomics and developing new therapeutic modalities. Progress in patient care would benefit from additional predictive models germane for human disease mechanisms, tumor heterogeneity, and therapeutic responses. Toward this aim, this review documents comparative aspects of human and naturally occurring canine melanomas. Clinical presentation, pathology, therapies, and genetic alterations are highlighted in the context of current basic and translational research in comparative oncology. Somewhat distinct from sun exposure-related human cutaneous melanomas, there is growing evidence that a variety of gene copy number alterations and protein structure/function mutations play roles in canine melanomas, in circumstances more analogous to human mucosal melanomas and to some extent other melanomas with murine sarcoma viral oncogene homolog B (BRAF), Neuroblastoma RAS Viral (V-Ras) Oncogene Homolog (NRAS), and neurofibromin 1 tumor suppressor NF1 triple wild-type genotype. Gaps in canine genome annotation, as well as an insufficient number and depth of sequences covered, remain considerable barriers to progress and should be collectively addressed. Preclinical approaches can be designed to include canine clinical trials addressing immune modulation as well as combined-targeted inhibition of Rat Sarcoma Superfamily/Mitogen-activated protein kinase (RAS/MAPK) and/or Phosphatidylinositol-3-Kinase/Protein Kinase B/Mammalian target of rapamycin (PI3K/AKT/mTOR) signal transduction, pathways frequently activated in both human and canine melanomas. Future investment should be aimed towards improving understanding of canine melanoma as a predictive preclinical surrogate for human melanoma and for mutually benefiting these uniquely co-dependent species.
An ωω\omega-Algebra for Real-Time Energy Problems.

We develop a $^*$-continuous Kleene $\omega$-algebra of real-time energy functions. Together with corresponding automata, these can be used to model systems which can consume and regain energy (or other types of resources) depending on available time. Using recent results on $^*$-continuous Kleene $\omega$-algebras and computability of certain manipulations on real-time energy functions, it follows that reachability and B\"uchi acceptance in real-time energy automata can be decided in a static way which only involves manipulations of real-time energy functions.
Transcriptional signatures of connectomic subregions of the human striatum

Functionally distinct regions of the brain are thought to possess a characteristic connectional fingerprint – a profile of incoming and outgoing connections that defines the function of that area. This observation has motivated efforts to subdivide cortical and subcortical areas using their patterns of connectivity. However, it remains unclear whether these connectomically-defined subregions of the brain can be distinguished at the molecular level. Here, we combine high-resolution diffusion-weighted magnetic resonance imaging with comprehensive transcriptomic data to show that connectomically-defined subregions of the striatum carry distinct transcriptional signatures. Using data-driven clustering of diffusion tractography, seeded from the striatum, in 100 healthy individuals, we identify a tripartite organization of the caudate and putamen that comprises ventral, dorsal, and caudal subregions. We then use microarray data of gene expression levels in 19 343 genes, taken from 98 tissue samples distributed throughout the striatum, to accurately discriminate the three connectomically-defined subregions with 80-90% classification accuracy using linear support vector machines. This classification accuracy was robust at the group and individual level. Genes contributing strongly to the classification were enriched for gene ontology categories including dopamine signaling, glutamate secretion, response to amphetamine, and metabolic pathways, and were implicated in risk for disorders such as schizophrenia, autism, and Parkinson’s disease. Our findings highlight a close link between regional variations in transcriptional activity and interregional connectivity in the brain, and suggest that there may be a strong genomic signature of connectomically-defined subregions of the brain.