Miracle-dz/UniFAR-FTUs huggingface dataset:
An efficient geometric algorithm to compute time-optimal trajectories for a car-like robot

This paper addresses the problem of computing a time-optimal trajectory between two configurations of a car- like robot. Since 1990, two remarkable results of this problem have been achieved: the sufficient family containing all types of optimal trajectories between any two configurations, and then the optimal synthesis determining a type of optimal trajectories for two specified configurations. Our contribution is to propose an algorithm which can determine a precise trajectory to link two specified configurations. Moreover, this algorithm has three features: first it can achieve an optimal trajectory ending at the exact final configuration; second it is complete, i.e. it allows to determine an optimal trajectory to link any two configurations; and third it has very low computational cost. The rules for designing this algorithm result from a new geometric reasoning in the switching space, which is another contribution of this paper.
Immunization with centrin-Deficient Leishmania braziliensis Does Not Protect against Homologous Challenge

Immunization with various Leishmania species lacking centrin induces robust immunity against a homologous and heterologous virulent challenge, making centrin mutants a putative candidate for a leishmaniasis vaccine. Centrin is a calcium-binding cytoskeletal protein involved in centrosome duplication in higher eukaryotes and Leishmania spp. lacking centrin are unable to replicate in vivo and are non-pathogenic. We developed a centrin-deficient Leishmania braziliensis (LbCen−/−) cell line and confirmed its impaired survival following phagocytosis by macrophages. Upon experimental inoculation into BALB/c mice, LbCen−/− failed to induce lesions and parasites were rapidly eliminated. The immune response following inoculation with LbCen−/− was characterized by a mixed IFN-γ, IL-4, and IL-10 response and did not confer protection against L. braziliensis infection, distinct from L. major, L. donovani, and L mexicana centrin-deficient mutants. A prime-boost strategy also did not lead to a protective immune response against homologous challenge. On the contrary, immunization with centrin-deficient L. donovani (LdonCen−/−) cross-protected against L. braziliensis challenge, illustrating the ability of LdonCen−/− to induce the Th1-dominant protective immunity needed for leishmaniasis control. In conclusion, while centrin deficiency in L. braziliensis causes attenuation of virulence, and disrupts the ability to cause disease, it fails to stimulate a protective immune response.
Activity Based Sector Synchronisation: Efficient Transfer of Disk-State for WAN Live Migration

Live migration of virtual machines is now commonplace but the issue of synchronising storage remains an obstacle to wide-area migration between datacentres. We discuss the range of possible designs for synchronising disk images and argue that we have to be adaptive at the sector level to efficiently transfer disk-state to the destination. We show, using a number of production workloads, that delaying the transmission of "hot"sectors can achieve considerable bandwidth reduction over anaaive eager strategy. We introduce the Activity Based Sector Synchronisation (ABSS) algorithm and show by trace-drivensimulations that ABSS is able to deliver a useful trade-off with a data transmission overhead between 0.3% and 2.4% of a gigabit link whilst incurring in the majority of cases a migration latency of less than 1.1 s.
Novel Small Molecule Inhibitors of TLR7 and TLR9: Mechanism of Action and Efficacy In Vivo

The discovery that circulating nucleic acid-containing complexes in the serum of autoimmune lupus patients can stimulate B cells and plasmacytoid dendritic cells via Toll-like receptors 7 and 9 suggested that agents that block these receptors might be useful therapeutics. We identified two compounds, AT791 {3-[4-(6-(3-(dimethylamino)propoxy)benzo[d]oxazol-2-yl)phenoxy]-N,N-dimethylpropan-1-amine} and E6446 {6-[3-(pyrrolidin-1-yl)propoxy)-2-(4-(3-(pyrrolidin-1-yl)propoxy)phenyl]benzo[d]oxazole}, that inhibit Toll-like receptor (TLR)7 and 9 signaling in a variety of human and mouse cell types and inhibit DNA-TLR9 interaction in vitro. When administered to mice, these compounds suppress responses to challenge doses of cytidine-phosphate-guanidine (CpG)–containing DNA, which stimulates TLR9. When given chronically in spontaneous mouse lupus models, E6446 slowed development of circulating antinuclear antibodies and had a modest effect on anti–double-stranded DNA titers but showed no observable impact on proteinuria or mortality. We discovered that the ability of AT791 and E6446 to inhibit TLR7 and 9 signaling depends on two properties: weak interaction with nucleic acids and high accumulation in the intracellular acidic compartments where TLR7 and 9 reside. Binding of the compounds to DNA prevents DNA-TLR9 interaction in vitro and modulates signaling in vivo. Our data also confirm an earlier report that this same mechanism may explain inhibition of TLR7 and 9 signaling by hydroxychloroquine (Plaquenil; Sanofi-Aventis, Bridgewater, NJ), a drug commonly prescribed to treat lupus. Thus, very different structural classes of molecules can inhibit endosomal TLRs by essentially identical mechanisms of action, suggesting a general mechanism for targeting this group of TLRs.
Extracorporeal membrane oxygenation in an HIV-positive man with severe acute respiratory distress syndrome secondary to pneumocystis and cytomegalovirus pneumonia

The management of critically ill human immunodeficiency virus (HIV)-positive patients is challenging; however, intensive care unit-related mortality has declined significantly in recent years. There are 10 case reports in the literature of extracorporeal membrane oxygenation (ECMO) use in HIV-positive patients, of whom seven survived to hospital discharge. We describe a 33-year-old Brazilian man who presented with Pneumocystis jirovecii pneumonia and severe hypoxic respiratory failure. He developed refractory acute respiratory distress syndrome (ARDS) and was commenced on veno-venous ECMO. He was successfully decannulated following 21 days of ECMO and survived to hospital discharge. Despite poor evidence surrounding the use of ECMO in immunocompromised patients, it is evident that ECMO could represent an important rescue therapy in HIV-positive patients with refractory ARDS.
A Meta-Analysis on the Effectiveness of Gratitude Promotion Programs for South Korean College Students

This study delves into the importance and consequences of gratitude promotion programs for South Korean college students. It uses meta-analyses to evaluate the effects of such programs on this demographic, shedding light on their significance and implications. To that end, we selected 11 papers in which 683 persons participated as study subjects, analyzing them using the PRISMA methodology. We observed an overall effect size of 0.6671, categorized as above medium. The effect sizes of the sub-areas were cognitive (d = 1.37), emotional (d = 0.60), and behavioral (d = 0.77), with the cognitive area exhibiting the largest effect size. When categorized by program type, the effect size (d = 0.85) for the program involving gratitude practice and gratitude recording surpassed the effect size (d = 0.77) of the programs where participants solely engaged in gratitude recording. According to program execution durations, the largest effect size (d = 1.61) appeared in the group that executed the program for the longest period of at least 16 weeks. This study highlights the areas where gratitude promotion programs for college students prove to be most effective. These findings offer valuable insights for tailoring and developing gratitude promotion programs in the future.
Catalogo PArametrico dei Terremoti Italiani, versione CPTI11

The Italian Parametric Earthquake Catalogue (CPTI, Catalogo Parametrico dei Terremoti Italiani) represents the most extensive and reliable source of parameters for earthquakes in Italy and surrounding areas. CPTI15 is the fourth release of the CPTI series, the first dating back to 1999, and provides the most advanced and updated sets of macroseismic and instrumental data and parameters, for Italian earthquakes with maximum intensity I ≥ 5 or magnitude Mw ≥ 4.0 in the period 1000-2014. The catalogue lists 4584 events, 70% of which are based on the macroseismic datapoints provided by the Italian Macroseismic Database DBMI15. If available, both macroseismic and instrumental parameters are provided, together with a set of “preferred ones”, which consist of a selection between the macroseismic and the instrumental epicentres, and the weighted average of the macroseismic and instrumental magnitudes.
Effect of a corticotropin releasing hormone receptor antagonist on colonic sensory and motor function in patients with irritable bowel syndrome

Background and aims: Corticotropin releasing hormone (CRH) is a major mediator of the stress response in the brain-gut axis. Irritable bowel syndrome (IBS) is presumed to be a disorder of the brain-gut link associated with an exaggerated response to stress. We hypothesised that peripheral administration of α-helical CRH (αhCRH), a non-selective CRH receptor antagonist, would improve gastrointestinal motility, visceral perception, and negative mood in response to gut stimulation in IBS patients. Methods: Ten normal healthy subjects and 10 IBS patients, diagnosed according to the Rome II criteria, were studied. The tone of the descending colon and intraluminal pressure of the sigmoid colon were measured at baseline, during rectal electrical stimulation (ES), and at recovery after administration of saline. Visceral perception after colonic distension or rectal ES was evaluated as threshold values on an ordinate scale. The same measurements were repeated after administration of αhCRH (10 μg/kg). Results: ES induced significantly higher motility indices of the colon in IBS patients compared with controls. This response was significantly suppressed in IBS patients but not in controls after administration of αhCRH. Administration of αhCRH induced a significant increase in the barostat bag volume of controls but not in that of IBS patients. αhCRH significantly reduced the ordinate scale of abdominal pain and anxiety evoked by ES in IBS patients. Plasma adrenocorticotropic hormone and serum cortisol levels were generally not suppressed by αhCRH. Conclusion: Peripheral administration of αhCRH improves gastrointestinal motility, visceral perception, and negative mood in response to gut stimulation, without affecting the hypothalamo-pituitary-adrenal axis in IBS patients.
progressiveMauve: Multiple Genome Alignment with Gene Gain, Loss and Rearrangement

Background Multiple genome alignment remains a challenging problem. Effects of recombination including rearrangement, segmental duplication, gain, and loss can create a mosaic pattern of homology even among closely related organisms. Methodology/Principal Findings We describe a new method to align two or more genomes that have undergone rearrangements due to recombination and substantial amounts of segmental gain and loss (flux). We demonstrate that the new method can accurately align regions conserved in some, but not all, of the genomes, an important case not handled by our previous work. The method uses a novel alignment objective score called a sum-of-pairs breakpoint score, which facilitates accurate detection of rearrangement breakpoints when genomes have unequal gene content. We also apply a probabilistic alignment filtering method to remove erroneous alignments of unrelated sequences, which are commonly observed in other genome alignment methods. We describe new metrics for quantifying genome alignment accuracy which measure the quality of rearrangement breakpoint predictions and indel predictions. The new genome alignment algorithm demonstrates high accuracy in situations where genomes have undergone biologically feasible amounts of genome rearrangement, segmental gain and loss. We apply the new algorithm to a set of 23 genomes from the genera Escherichia, Shigella, and Salmonella. Analysis of whole-genome multiple alignments allows us to extend the previously defined concepts of core- and pan-genomes to include not only annotated genes, but also non-coding regions with potential regulatory roles. The 23 enterobacteria have an estimated core-genome of 2.46Mbp conserved among all taxa and a pan-genome of 15.2Mbp. We document substantial population-level variability among these organisms driven by segmental gain and loss. Interestingly, much variability lies in intergenic regions, suggesting that the Enterobacteriacae may exhibit regulatory divergence. Conclusions The multiple genome alignments generated by our software provide a platform for comparative genomic and population genomic studies. Free, open-source software implementing the described genome alignment approach is available from http://gel.ahabs. wisc.edu/mauve.
Impaired Stress-Coping and Fear Extinction and Abnormal Corticolimbic Morphology in Serotonin Transporter Knock-Out Mice

A lesser-expressing form of the human 5-HT transporter (5-HTT) gene has been associated with increased fear and anxiety and vulnerability to the effects of stress. These phenotypic abnormalities are linked to functional and anatomical disturbances in a neural pathway connecting the prefrontal cortex (PFC) and amygdala. Likewise, rodent and nonhuman primate studies indicate a major role for PFC and amygdala in the mediation of fear- and stress-related behaviors. We used a 5-HTT knock-out (KO) mouse to examine the effects of genetically driven loss of 5-HTT function for the following: (1) depression-related behavior in response to repeated stress, and pavlovian fear conditioning, extinction, and extinction recall; and (2) dendritic morphology and spine density of Golgi-stained pyramidal neurons in the infralimbic cortex (IL) and the basolateral amygdala (BLA). 5-HTT KO mice exhibited increased depressive-like immobility after repeated exposure to forced swim stress, compared with wild-type (WT) controls. Whereas fear conditioning and fear extinction was normal, 5-HTT KO mice exhibited a significant deficit in extinction recall. The apical dendritic branches of IL pyramidal neurons in 5-HTT KO mice were significantly increased in length relative to WT mice. Pyramidal neurons in BLA had normal dendritic morphology but significantly greater spine density in 5-HT KO mice compared with WT mice. Together, the present findings demonstrate a specific phenotypic profile of fear- and stress-related deficits in 5-HTT KO mice, accompanied by morphological abnormalities in two key neural loci. These data provide insight into the behavioral sequelae of loss of 5-HTT gene function and identify potential neural substrates underlying these phenotypes.
Scalable Planning with Tensorflow for Hybrid Nonlinear Domains

Given recent deep learning results that demonstrate the ability to effectively optimize high-dimensional non-convex functions with gradient descent optimization on GPUs, we ask in this paper whether symbolic gradient optimization tools such as Tensorflow can be effective for planning in hybrid (mixed discrete and continuous) nonlinear domains with high dimensional state and action spaces? To this end, we demonstrate that hybrid planning with Tensorflow and RMSProp gradient descent is competitive with mixed integer linear program (MILP) based optimization on piecewise linear planning domains (where we can compute optimal solutions) and substantially outperforms state-of-the-art interior point methods for nonlinear planning domains. Furthermore, we remark that Tensorflow is highly scalable, converging to a strong plan on a large-scale concurrent domain with a total of 576,000 continuous action parameters distributed over a horizon of 96 time steps and 100 parallel instances in only 4 minutes. We provide a number of insights that clarify such strong performance including observations that despite long horizons, RMSProp avoids both the vanishing and exploding gradient problems. Together these results suggest a new frontier for highly scalable planning in nonlinear hybrid domains by leveraging GPUs and the power of recent advances in gradient descent with highly optimized toolkits like Tensorflow.
Depletion of mitochondrial DNA copies/cell in peripheral blood mononuclear cells in HIV‐1‐infected treatment‐naïve patients

Mitochondrial toxicity is believed to be the main reason for adverse effects related to nucleoside reverse transcriptase inhibitors (NRTIs). The aim of the present study was to compare mitochondrial toxicity in NRTI‐treated HIV‐positive patients, HIV‐positive treatment‐naïve patients and HIV‐negative controls by comparing mitochondrial DNA (mtDNA) copies/cell in peripheral blood mononuclear cells (PBMCs) and lactate/pyruvate (L/P) ratios in the different groups.
A multi-level radiation transfer solution for 3D landscape

A multi-level radiation transfer method was proposed to simulate directional reflectance and images for 3D landscapes. This study emphasizes a unified framework to generate multi-level structures from leaf to landscape. Radiosity is adapted to improve calculation efficiency. The program was preliminarily evaluated and further applied to analyze how directional reflectance varies with fragmentation and terrain relief. Results indicate that grass-dominated landscapes are more likely to be affected on directional reflectance feature by fragmented forest patches. Also, topographical relief can strongly enhance the hotspot effect and directional variations in the solar principal plane.
Principal Warps: Thin-Plate Splines and the Decomposition of Deformations

The decomposition of deformations by principal warps is demonstrated. The method is extended to deal with curving edges between landmarks. This formulation is related to other applications of splines current in computer vision. How they might aid in the extraction of features for analysis, comparison, and diagnosis of biological and medical images in indicated. >
Databases for sea surface paleotemperature based on geochemical proxies from marine sediments: implications for model-data comparisons

The Paleoclimate Model Intercomparison Project (PMIP) aims to simulate the response of Earth’s climate system to changes in different climate forcing factors, focusing on six key intervals of the geological past (the mid-Piacenzian Warm Period at ~3.3-3.0 Ma, the last interglacial period at ~127 ka, the last glacial maximum at ~21 ka, the mid-Holocene at ~6 ka, the last millennium i.e. the 850-1850 Common Era (CE) time window, as well as the last glacial termination, i.e. the ~21-9 ka time window). Model evaluation is ultimately achieved via model-data comparison exercises, and such diagnoses rely on databases of proxy-based paleoclimate reconstructions available in the literature. In this context, we provide a review of the main geochemical sea surface temperature (SST) proxies (namely foraminiferal Mg/Ca ratio, the UK’37, and the TEX86) that are routinely used to aliment databases used in model-data comparisons, focusing on proxy systematics and specificities that may affect or bias SSTs reconstructed with each of these proxies. We then go on to discuss notorious mismatches between SST estimates derived from different proxies for all periods studied in PMIP, and aim to provide guidance for a better interpretation of these model-data mismatches. This review is deliberately aimed at helping the paleoclimate modeling community to better appraise how information on past SST variability is transferred to the marine geological record. In particular, when SST estimates based on different proxies provide contrasting SST signals, we stress the importance of looking at those contrasting signals through the prism of the ecology of the organisms at the origin of the SST proxies.
Human Survivin Is a Kinetochore-Associated Passenger Protein

Survivin, a dimeric baculovirus inhibitor of apoptosis repeat (BIR) motif protein that is principally expressed in G2 and mitosis, has been associated with protection against apoptosis of cells that exit mitosis aberrantly. Mammalian survivin has been reported to associate with centrosomes and with the mitotic spindle. We have expressed a human hemagglutinin-tagged survivin plasmid to determine its localization, and find instead that it clearly acts as a passenger protein. In HeLa cells, survivin first associates with the kinetochores, and then translocates to the spindle midzone during anaphase and, finally, to the midbody during cell cleavage. Its localization is similar to that of TD-60, a known passenger protein. Both a point mutation in the baculovirus IAP repeat motif (C84A) and a COOH-terminal deletion mutant (Δ106) of survivin fail to localize to either kinetochores or midbodies, but neither interferes with cell cleavage. The interphase localization of survivin is cell cycle regulated since in permanently transfected NIH3T3 cells it is excluded from the nuclei until G2, where it localizes with centromeres. Survivin remains associated with mitotic kinetochores when microtubule assembly is disrupted and its localization is thus independent of microtubules. We conclude that human survivin is positioned to have an important function in the mechanism of cell cleavage.
A VIEW of Russian: Visual Input Enhancement and Adaptive Feedback

We explore the challenges and opportunities which arise in developing automatic visual input enhancement activities for Russian with a focus on target selection and adaptive feedback. Russian, a language with a rich fusional morphology, has many syntactically relevant forms that are not transparent to the language learner, which makes it a good candidate for visual input enhancement (VIE). VIE essentially supports incidental focus on form by increasing the salience of language forms to support noticing by the learner. The freely available VIEW system (Meurers et al., 2010) was designed to automatically generate VIE activities from any web content. We extend VIEW to Russian and discuss connected research issues regarding target selection, ambiguity management, prompt generation, and distractor generation. We show that the same information and techniques used for target selection can often be repurposed for adaptive feedback. Authentic Text ICALL (ATICALL) systems incorporating only native-language NLP, without the NLP analysis specific to learner language that is characteristic of Intelligent Language Tutoring Systems (ILTS), thus can support some forms of adaptive feedback. ATICALL and ILTS represent a spectrum of possibilities rather than two categorically distinct enterprises.
Myhre syndrome

Myhre syndrome is a condition involving short stature, characteristic facial features, hearing loss, limited joint mobility, a buildup of scar tissue (fibrosis) in the skin and internal organs, and other problems affecting multiple body systems. Affected individuals often have problems with the heart and blood vessels (cardiovascular system), the lungs and airways (respiratory system), and the skeletal system. The cardiovascular and respiratory problems gradually get worse and can lead to potentially life-threatening complications. People with Myhre syndrome may have an increased risk of developing cancerous or noncancerous tumors, including cancer of the lining of the uterus (endometrial cancer).