Miracle-dz/UniFAR-FTUs huggingface dataset:
A GPU-accelerated continuous and discontinuous Galerkin non-hydrostatic atmospheric model

We present a Graphics Processing Unit (GPU)-accelerated nodal discontinuous Galerkin method for the solution of the three-dimensional Euler equations that govern the motion and thermodynamic state of the atmosphere. Acceleration of the dynamical core of atmospheric models plays an important practical role in not only getting daily forecasts faster, but also in obtaining more accurate (high resolution) results within a given simulation time limit. We use algorithms suitable for the single instruction multiple thread architecture of GPUs to accelerate our model by two orders of magnitude relative to one core of a CPU. Tests on one node of the Titan supercomputer show a speedup of up to 15 times using the K20X GPU as compared to that on the 16-core AMD Opteron CPU. The scalability of the multi-GPU implementation is tested using 16,384 GPUs, which resulted in a weak scaling efficiency of about 90%. Finally, the accuracy and performance of our GPU implementation is verified using several benchmark problems representative of different scales of atmospheric dynamics.
Digital centric multi-gigabit SerDes design and verification

Advances in semiconductor manufacturing still lead to ever decreasing feature sizes and constantly allow higher degrees of integration in application specific integrated circuits (ASICs). Therefore the bandwidth requirements on the external interfaces of such systems on chips (SoC) are steadily growing. Yet, as the number of pins on these ASICs is not increasing in the same pace - known as pin limitation - the bandwidth per pin has to be increased. SerDes (Serializer/Deserializer) technology, which allows to transfer data serially at very high data rates of 25Gbps and more is a key technology to overcome pin limitation and exploit the computing power that can be achieved in todays SoCs. As such SerDes blocks together with the digital logic interfacing them form complex mixed signal systems, verification of performance and functional correctness is very challenging. In this thesis a novel mixed-signal design methodology is proposed, which tightly couples model and implementation in order to ensure consistency throughout the design cycles and hereby accelerate the overall implementation flow. A tool flow that has been developed is presented, which integrates well into state of the art electronic design automation (EDA) environments and enables the usage of this methodology in practice. Further, the design space of todays high-speed serial links is analyzed and an architecture is proposed, which pushes complexity into the digital domain in order to achieve robustness, portability between manufacturing processes and scaling with advanced node technologies. The all digital phase locked loop (PLL) and clock data recovery (CDR), which have been developed are described in detail. The developed design flow was used for the implementation of the SerDes architecture in a 28nm silicon process and proved to be indispensable for future projects.
A new species of Escallonia (Escalloniaceae) from the inter-Andean tropical dry forests of Bolivia

Over the last two decades, renewed fieldwork in poorly explored areas of the tropical Andes has dramatically increased the comparative material available to study patterns of inter- and intraspecific variation in tropical plants. In the course of a comprehensive study of the genus Escallonia, we found a group of specimens with decumbent branching, small narrowly elliptic leaves, inflorescences with up to three flowers, and flowers with red petals. This unique combination of traits was not present in any known species of the genus. To evaluate the hypothesis that these specimens belonged to a new species, we assessed whether morphological variation between the putative new species and all currently known Escallonia species was discontinuous. The lack of overlap in tolerance regions for vegetative and reproductive traits combined with differences in habit, habitat, and geographic distribution supported the hypothesis of the new species, which we named Escallonia harrisii. The new species grows in sandstone inter-Andean ridges and cliffs covered with dry forest, mostly on steep slopes between 1,300–2,200 m in southern Bolivia. It is readily distinct in overall leaf and flower morphology from other Escallonia species in the region, even though it does not grow in sympatry with other species. Because E. harrisii is locally common it may not be threated at present, but due to its restricted geographic distribution and the multiple threats of the tropical dry forests it could become potentially vulnerable.
Sjögren's Syndrome: Concerted Triggering of Sicca Conditions

Aim The aim of this study was to evaluate the expression of persistence of mumps virus and some cells that interact with viral infection in the focus of the autoimmune epithelitis and peripheral blood of Sjögren's syndrome patients in comparison to patients with rheumatoid arthritis (RA) and nonautoimmune sicca syndrome (nSS). Materials and Methods 126 patients (119 women and 7 men) were grouped into four groups: (1) patients with primary Sjögren's syndrome (pSS), (2) patients with secondary Sjögren's syndrome due to rheumatoid arthritis (sSS), (3) patients with rheumatoid arthritis (RA), and (4) patients with nonautoimmune sicca syndrome (nSS). Immunohistochemical analysis of immune response to the suggested silent persistence of mumps virus in the minor labial salivary gland biopsies and flow cytometric analysis of blood cells was done. Results Immunohistochemical signs of mumps virus persistence were found in the minor salivary glands of all study groups. Also, a significantly different immune response to virus infection (protein IFI16, interferons gamma and beta, dendritic cells, and receptor for natural killers) was revealed in the minor salivary glands of the study groups. Cytometric analysis of the blood cells revealed a dropping amount of circulating natural killers and dendritic cells in patients with SS. Significant correlations between immunohistochemical staining and serological findings were revealed. Conclusions Abundant immunohistochemical signs of mumps virus protein in the salivary glands and depletion of circulating immune cells make a background for thought of presumable mumps or/and other virus participation in epithelial damage causing sicca syndrome in predisposed patients.
Inhibition of Hedgehog signaling reprograms the dysfunctional immune microenvironment in breast cancer

ABSTRACT Host responses to tumor cells include tumor suppressing or promoting mechanisms. We sought to detail the effect of Hedgehog (Hh) pathway inhibition on the composition of the mammary tumor immune portfolio. We hypothesized that Hh signaling mediates a crosstalk between breast cancer cells and macrophages that dictates alternative polarization of macrophages and consequently supports a tumor-promoting microenvironment. We used an immunocompetent, syngeneic mouse mammary cancer model to inhibit Hh signaling with the pharmacological inhibitor, Vismodegib. Using molecular and functional assays, we identified that Hedgehog (Hh) signaling mediates a molecular crosstalk between mammary cancer cells and macrophages that culminates in alternative polarization of macrophages. We carried out an unbiased kinomics and genomics assessment to unravel changes in global kinomic and gene signatures impacted by Hh signaling. Our investigations reveal that in an immunocompetent mammary cancer model, the administration of Vismodegib led to changes in the portfolio of tumor-infiltrating immune cells. This was characterized by a marked reduction in immune-suppressive innate and adaptive cells concomitant with an enrichment of cytotoxic immune cells. Breast cancer cells induce M2 polarization of macrophages via a crosstalk mediated by Hh ligands that alters critical kinomic and genomic signatures. Macrophage depletion improved the benefit of Hedgehog inhibition on eliciting an immunogenic, pro-inflammatory profile. We define a novel role for Hh signaling in disabling anti-tumor immunity. Inhibition of Hh signaling presents with dual advantages of tumor cell-targeting as well as re-educating a dysfunctional tumor microenvironment.
Pain management in acute otitis media: a qualitative study exploring GPs’ views and expectations parallel to a trial of an educational intervention

Background Optimal pain management is accepted as the cornerstone of acute otitis media (AOM) management, but analgesics are neither prescribed routinely nor explicitly recommended in day-to-day practice. Aim To explore GPs views on and expectations regarding pain management in children with AOM, and how a multifaceted educational intervention aimed at optimising pain management shapes these perceptions. Design & setting Qualitative study conducted alongside a cluster randomised controlled trial (cRCT), the PIMPOM study, in the Netherlands. Method Twelve GPs were purposefully sampled from primary care centres allocated to the intervention group and were interviewed, using semi-structured, audio-recorded interviews. The intervention comprised a blended GP educational programme (internet-based and face-to-face training) aimed at discussing pain management proactively with parents using a parent information leaflet, and prescribing paracetamol and ibuprofen according to current guidelines. Interviews were transcribed verbatim and analysed thematically by a multidisciplinary team. Results GPs considered AOM a very painful condition. Initially, GPs felt unable to offer adequate treatment for AOM-related ear pain. The intervention provided tools, such as knowledge, communication skills, and an information leaflet, which reduced their feelings of helplessness and empowered them to manage childhood AOM more adequately. GPs indicated that the intervention led to a shift in focus from treating the infection with antibiotics to treating symptoms with analgesics. There was a general lack of knowledge about the possibility of prescribing ibuprofen to children. GPs expressed mixed views on prescribing this drug to children. Conclusion A primary-care based multifaceted educational intervention aimed at optimising pain management in childhood AOM offered GPs tools to optimise management of this condition and changed GPs perceptions, namely from treating the infection with antibiotics to treating symptoms.
Safety and efficacy of Tet-regulated IL-12 expression in cancer-specific T cells

ABSTRACT We explored whether engineering of T cell specificity and effector function improves immunotherapy of solid tumors. Although IL-12 can enhance cancer immunity, a strategy of safe IL-12 delivery without toxicity is currently lacking. We engineered T cells to express IL-12 controlled by the NFAT promoter responsive to TCR stimulation, or by the Tet-On promoter responsive to doxycycline. In vivo, NFAT-engineered T cells caused lethal toxicity, while Tet-engineered T cells were safe in the absence of doxycycline. Combining gene transfer of the melanoma-specific TRP2-TCR with Tet-IL-12 engineering revealed that temporal induction of IL-12 was essential to inhibit the growth of B16F10 melanoma tumors. Induced IL-12 increased the number of tumor-infiltrating T cells and also prevented the down-modulation of the TRP2-TCR and the associated up-regulation of the PD1 marker that was observed in the absence of IL-12. In addition, temporal induction of IL-12 expression also increased the number of plasmacytoid DC in the tumor micro-environment. We show that repeated induction of IL-12 can be used to enhance control of tumor growth without encountering systemic toxicity. The observation that TCR engineering combined with Tet-regulated IL-12 expression can achieve tumor immunity without the side effects that are usually associated with the in vivo use of IL-12 warrants translation of this concept into the clinic.
Maternal temperature exposure impairs emotional and cognitive responses and triggers dysregulation of neurodevelopment genes in fish

Fish are sensitive to temperature, but the intergenerational consequences of maternal exposure to high temperature on offspring behavioural plasticity and underlying mechanisms are unknown. Here we show that a thermal maternal stress induces impaired emotional and cognitive responses in offspring rainbow trout (Oncorhynchus mykiss). Thermal stress in mothers triggered the inhibition of locomotor fear-related responses upon exposure to a novel environment and decreased spatial learning abilities in progeny. Impaired behavioural phenotypes were associated with the dysregulation of several genes known to play major roles in neurodevelopment, including auts2 (autism susceptibility candidate 2), a key gene for neurodevelopment, more specifically neuronal migration and neurite extension, and critical for the acquisition of neurocognitive function. In addition, our analysis revealed the dysregulation of another neurodevelopment gene (dpysl5) as well as genes associated with human cognitive disorders (arv1, plp2). We observed major differences in maternal mRNA abundance in the eggs following maternal exposure to high temperature indicating that some of the observed intergenerational effects are mediated by maternally-inherited mRNAs accumulated in the egg. Together, our observations shed new light on the intergenerational determinism of fish behaviour and associated underlying mechanisms. They also stress the importance of maternal history on fish behavioural plasticity.
Identification, expression, and phylogenetic analyses of terpenoid biosynthesis-related genes in secondary xylem of loblolly pine (Pinus taeda L.) based on transcriptome analyses

Loblolly pine (Pinus taeda L.) is one of the most important species for oleoresin (a mixture of terpenoids) in South China. The high oleoresin content of loblolly pine is associated with resistance to bark beetles and other economic benefits. In this study, we conducted transcriptome analyses of loblolly pine secondary xylem to gain insight into the genes involved in terpenoid biosynthesis. A total of 372 unigenes were identified as being critical for oleoresin production, including genes for ATP-binding cassette (ABC) transporters, the cytochrome P450 (CYP) protein family, and terpenoid backbone biosynthesis enzymes. Six key genes involved in terpenoid biosynthetic pathways were selected for multiple sequence alignment, conserved motif prediction, and phylogenetic and expression profile analyses. The protein sequences of all six genes exhibited a higher degree of sequence conservation, and upstream genes were relatively more conserved than downstream genes in terpenoid biosynthetic pathways. The N-terminal regions of these sequences were less conserved than the C-terminal ends, as the N-terminals were quite diverse in both length and composition. The phylogenetic analyses revealed that most genes originated from gene duplication after species divergence, and partial genes exhibited incomplete lineage sorting. In addition, the expression profile analyses showed that all six genes exhibited high expression levels during the high-oleoresin-yielding phase.
High-resolution maps of Swiss apiaries and their applicability to study spatial distribution of bacterial honey bee brood diseases

Honey bees directly affect and are influenced by their local environment, in terms of food sources, pollinator densities, pathogen and toxin exposure and climate. Currently, there is a lack of studies analyzing these data with Geographic Information Systems (GIS) to investigate spatial relationships with the environment. Particularly for inter-colonial pathogen transmission, it is known that the likelihood of a healthy colony to become infested (e.g., Varroosis) or infected (e.g., American foulbrood—AFB, European foulbrood—EFB) increases with higher colony density. Whether these transmission paths can actually be asserted at apiary level is largely unknown. Here, we unraveled spatial distribution and high-resolution density of apiaries and bacterial honey bee brood diseases in Switzerland based on available GIS data. Switzerland as ‘model country’ offers the unique opportunity to get apiary data since 2010 owing to compulsory registration for every beekeeper. Further, both destructive bee brood diseases (AFB and EFB) are legally notifiable in Switzerland, and EFB has an epizootic character for the last decades. As governmental data sets have to be ameliorated, raw data from the cantonal agricultural or veterinary offices have been included. We found a mean density of 0.56 apiaries per km2, and high resolution spatial analyzes showed strong correlation between density of apiaries and human population density as well as agricultural landscape type. Concerning two bacterial bee brood diseases (AFB, EFB), no significant correlation was detectable with density of apiaries on cantonal level, though a high correlation of EFB cases and apiary density became obvious on higher resolution (district level). Hence, Swiss EFB epizootics seem to have benefited from high apiary densities, promoting the transmission of pathogens by adult bees. The GIS-based method presented here, might also be useful for other bee diseases, anthropogenic or environmental factors affecting bee colonies.
Current Practice in the Management of Pulmonary Nodules Detected on Computed Tomography Chest Scans

Lung cancer is associated with high mortality. It can present as one or more pulmonary nodules identified on computed tomography (CT) chest scans. The National Lung Screening Trial has shown that the use of low-dose CT chest screening can reduce deaths due to lung cancer. High adherence to appropriate follow-up of positive results, including imaging or interventional approaches, is an important aspect of pulmonary nodule management. Our study is one of the first to evaluate the current practice in managing pulmonary nodules and to explore potential causes for nonadherence to follow-up. This is a retrospective analysis at St. Paul's Hospital, a tertiary healthcare center in Vancouver, British Columbia, Canada. We first identified CT chest scans between January 1 to June 30, 2014, that demonstrated one or more pulmonary nodules equal to or greater than 6 mm in diameter. We then looked for evidence of interventional (surgical resection or biopsy, or bronchoscopy for transbronchial biopsy and cytology) and radiological follow-up of the pulmonary nodule by searching on the province-wide CareConnect eHealth Viewer patient database. A total of 1614 CT reports were analyzed and 139 (8.6%) had a positive finding. Out of the 97 patients who received follow-up, 54.6% (N = 53) was referred for a repeat CT chest scan and 36.1% (N = 35) and 9.3% (N = 9) were referred for interventional biopsy and surgical resection, respectively. In our study, 30.2% (N = 42) of the patients with pulmonary nodules were nonadherent to follow-up. Despite the radiologist's recommendation for follow-up within a certain time interval, only 36% had repeat imaging in a timely manner. Our findings reflect the current practice in the management of pulmonary nodules and suggest that there is a need for improvement at our academic center. Adherence to follow-up is important for the potentially near-future implementation of lung cancer screening.
Geriatric Consultation Reduces High-risk Medication Usage at Discharge in Elderly Trauma Patients

Background Traumatic injury in a growing geriatric population is associated with higher mortality and complication rates. Geriatric consultation (GC) is vital in reducing risk factors that contribute to adverse outcomes. This study aims to determine if receiving a GC had an impact on high-risk medication usage. Methods Patients eligible for a GC, age ≥ 65, and length of stay > two days, were identified via a chart review from July 2013 to July 2014 at a Level II trauma center. This population was divided into those with and without a GC. Data collected included demographics, injury severity, medications, delirium, mortality, and readmissions. High-risk medications were defined using the Beers Criteria. Statistical analysis involved using appropriate standard tests to compare groups, including multivariate logistic regression. Results Forty-nine of a total of 104 patients received a GC. Groups were comparable on injury severity score, co-morbidities, and high-risk medication use upon admissions. The GC group was 74% less likely to be discharged on high-risk medications than the non-GC group. Conclusion GC in elderly trauma patients reduces high-risk medication use upon discharge. Further studies are needed to explore how GC impacts readmission rates and mortality. A multidisciplinary trauma team, including a geriatrician, must exist to address the unique medical, psychological, functional, and social issues of a growing, aged trauma population.
Network Plasticity Involved in the Spread of Neural Activity Within the Rhinal Cortices as Revealed by Voltage-Sensitive Dye Imaging in Mouse Brain Slices

The rhinal cortices, such as the perirhinal cortex (PC) and the entorhinal cortex (EC), are located within the bidirectional pathway between the neocortex and the hippocampus. Physiological studies indicate that the perirhinal transmission of neocortical inputs to the EC occurs at an extremely low probability, though many anatomical studies indicated strong connections exist in the pathway. Our previous study in rat brain slices indicated that an increase in excitability in deep layers of the PC/EC border initiated the neural activity transfer from the PC to the EC. In the present study, we hypothesized that such changes in network dynamics are not incidental observations but rather due to the plastic features of the perirhinal network, which links with the EC. To confirm this idea, we analyzed the network properties of neural transmission throughout the rhinal cortices and the plastic behavior of the network by performing a single-photon wide-field optical recording technique with a voltage-sensitive dye (VSD) in mouse brain slices of the PC, the EC, and the hippocampus. The low concentration of 4-aminopyridine (4-AP; 40 μM) enhanced neural activity in the PC, which eventually propagated to the EC via the deep layers of the PC/EC border. Interestingly, washout of 4-AP was unable to reverse entorhinal activation to the previous state. This change in the network property persisted for more than 1 h. This observation was not limited to the application of 4-AP. Burst stimulation to neurons in the perirhinal deep layers also induced the same change of network property. These results indicate the long-lasting modification of physiological connection between the PC and the EC, suggesting the existence of plasticity in the perirhinal-entorhinal network.
Christians and Buddhists Are Comparably Happy on Twitter: A Large-Scale Linguistic Analysis of Religious Differences in Social, Cognitive, and Emotional Tendencies

Are different religions associated with different social, cognitive, and emotional tendencies? Although major world religions are known to encourage social interactions and help regulate emotions, it is less clear to what extent adherents of various religions differ in these dimensions in daily life. We thus carried out a large-scale sociolinguistic analysis of social media messages of Christians and Buddhists living in the United States. After controlling for age and gender effects on linguistic patterns, we found that Christians used more social words and fewer cognitive words than Buddhists. Moreover, adherents of both religions, similarly used more positive than negative emotion words on Twitter, although overall, Christians were slightly more positive in verbal emotional expression than Buddhists. These sociolinguistic patterns of actual rather than ideal behaviors were also paralleled by language used in the popular sacred texts of Christianity and Buddhism, with the exception that Christian texts contained more negative and fewer positive emotion words than Buddhist texts. Taken together, our results suggest that the direct or indirect influence of religious texts on the receivers of their messages may partially, but not fully, account for the verbal behavior of religious adherents.