Miracle-dz/UniFAR-FTUs huggingface dataset:
Resset: A Recurrent Model for Sequence of Sets with Applications to Electronic Medical Records

Modern healthcare is ripe for disruption by AI. A game changer would be automatic understanding the latent processes from electronic medical records, which are being collected for billions of people worldwide. However, these healthcare processes are complicated by the interaction between at least three dynamic components: the illness which involves multiple diseases, the care which involves multiple treatments, and the recording practice which is biased and erroneous. Existing methods are inadequate in capturing the dynamic structure of care. We propose Resset, an end-to-end recurrent model that reads medical record and predicts future risk. The model adopts the algebraic view in that discrete medical objects are embedded into continuous vectors lying in the same space. We formulate the problem as modeling sequences of sets, a novel setting that have rarely, if not, been addressed. Within Resset, the bag of diseases recorded at each clinic visit is modeled as function of sets. The same hold for the bag of treatments. The interaction between the disease bag and the treatment bag at a visit is modeled in several, one of which as residual of diseases minus the treatments. Finally, the health trajectory, which is a sequence of visits, is modeled using a recurrent neural network. We report results on over a hundred thousand hospital visits by patients suffered from two costly chronic diseases -- diabetes and mental health. Resset shows promises in multiple predictive tasks such as readmission prediction, treatments recommendation and diseases progression.
Tight Hardness for Shortest Cycles and Paths in Sparse Graphs

Fine-grained reductions have established equivalences between many core problems with $\tilde{O}(n^3)$-time algorithms on $n$-node weighted graphs, such as Shortest Cycle, All-Pairs Shortest Paths (APSP), Radius, Replacement Paths, Second Shortest Paths, and so on. These problems also have $\tilde{O}(mn)$-time algorithms on $m$-edge $n$-node weighted graphs, and such algorithms have wider applicability. Are these $mn$ bounds optimal when $m \ll n^2$? Starting from the hypothesis that the minimum weight $(2\ell+1)$-Clique problem in edge weighted graphs requires $n^{2\ell+1-o(1)}$ time, we prove that for all sparsities of the form $m = \Theta(n^{1+1/\ell})$, there is no $O(n^2 + mn^{1-\epsilon})$ time algorithm for $\epsilon>0$ for \emph{any} of the below problems: Minimum Weight $(2\ell+1)$-Cycle in a directed weighted graph, Shortest Cycle in a directed weighted graph, APSP in a directed or undirected weighted graph, Radius (or Eccentricities) in a directed or undirected weighted graph, Wiener index of a directed or undirected weighted graph, Replacement Paths in a directed weighted graph, Second Shortest Path in a directed weighted graph, Betweenness Centrality of a given node in a directed weighted graph. That is, we prove hardness for a variety of sparse graph problems from the hardness of a dense graph problem. Our results also lead to new conditional lower bounds from several related hypothesis for unweighted sparse graph problems including $k$-cycle, shortest cycle, Radius, Wiener index and APSP.
SURFACE HARDNESS OF ORIENTAL BEECH PRE-IMPREGNATED WITH CCB BEFORE VARNISH COATING AFTER ACCELERATED LIGHTFASTNESS AND ACCELERATED AGING

This study was designed to determine accelerated lightfastness and accelerated aging investigating the surface hardness performance of a polyurethane varnish (PV) and an alkyd based synthetic varnish (SV) coated Oriental beech (Fagus orientalis L.) wood that is preimpregnated with CCB (chromium-copper-boron). Results showed that while accelerated lightfastness hardened the wood surface, accelerated aging remarkably softened it. CCB pre-impregnation before varnish coating caused increase in hardness of coated Oriental beech wood after both exposure conditions. Higher concentrations of CCB resulted in harder surfaces of Oriental beech wood.
Characterization of processing pores and their relevance to the strength in alumina ceramics

Characterization of bulk defects was successfully accomplished in alumina with a transmission optical microscope. The characterization technique used is based on the fact that many ceramics are essentially transparent. Most defects in this particular ceramic were found to be pore. Their size distribution was found to follow a simple power function. With these characteristics of defects, the strength distribution of the ceramics was calculated with Baratta’s model and compared to the measured strength of the ceramics. A good agreement was found between them when the pore was assumed to be accompanied with cracks 4 times the length of the grain size.
Amyloid Precursor Protein family as unconventional Go-coupled receptors and the control of neuronal motility

ABSTRACT Cleavage of the Amyloid Precursor Protein (APP) generates amyloid peptides that accumulate in Alzheimer Disease (AD), but APP is also upregulated by developing and injured neurons, suggesting that it regulates neuronal motility. APP can also function as a G protein-coupled receptor that signals via the heterotrimeric G protein Gαo, but evidence for APP-Gαo signaling in vivo has been lacking. Using Manduca as a model system, we showed that insect APP (APPL) regulates neuronal migration in a Gαo-dependent manner. Recently, we also demonstrated that Manduca Contactin (expressed by glial cells) induces APPL-Gαo retraction responses in migratory neurons, consistent with evidence that mammalian Contactins also interact with APP family members. Preliminary studies using cultured hippocampal neurons suggest that APP-Gαo signaling can similarly regulate growth cone motility. Whether Contactins (or other APP ligands) induce this response within the developing nervous system, and how this pathway is disrupted in AD, remains to be explored.
Cancer and inflammation

The relationship between inflammation and cancer has been recognized since the 17th century,1 and we now know much about the cells, cytokines and physiological processes that are central to both inflammation and cancer.2-9 Chronic inflammation can induce certain cancers,10-17 and solid tumors, in turn, can initiate and perpetuate local inflammatory processes that foster tumor growth and dissemination.5,18-20 Consequently, inflammatory pathways have been targeted in attempts to control cancer.21-23 Inflammation is a central aspect of the innate immune system's response to tissue damage or infection, and also facilitates the recruitment of circulating cells and antibodies of the adaptive immune response to the tissue. Components of the innate immune response carry out a robust, but sometimes overly‐conservative response, sacrificing specificity for the sake of preservation. Thus, when innate immunity goes awry, it can have profound implications. How the innate and adaptive immune systems cooperate to neutralize pathogens and repair damaged tissues is still an area of intense investigation. Further, how these systems can respond to cancer, which arises from normal ‘self’ cells that undergo an oncogenic transformation, has profound implications for cancer therapy. Recently, immunotherapies that activate adaptive immunity have shown unprecedented promise in the clinic, producing durable responses and dramatic increases in survival rate in patients with advanced stage melanoma.24-26 Consequently, the relationship between cancer and inflammation has now returned to the forefront of clinical oncology. WIREs Syst Biol Med 2017, 9:e1370. doi: 10.1002/wsbm.1370
Chill-Coma and Minimum Movement Temperatures of Stored-Product Beetles in Stored Wheat

ABSTRACT The minimum temperature at which stored-product insects can move inside stored grain bulks with different grain moisture contents is not known. The movement of adults of four storedproduct insects, Cryptolestes ferrugineus (Stephens), Tribolium castaneum (Herbst), Sitophilus oryzae (L.), and Sitophilus zeamais (Motschulsky), at low temperatures inside jars or bulks of wheat with 11.1 or 16.0% moisture content was measured. Spontaneous walking stops (SMh), CCT (no movement after shaken), and minimum movement (TMmin, caught in probe pitfall traps) temperatures were determined at stepped-decrease of temperature. The ranges of SMh, CCT, and TMmin temperatures of the four stored-products beetles were 4.0 to 9.0°C, 2.0 to 8.0°C, and 6.0 to 11.5°C, respectively. The TMmin was ∼3°C higher than the SMh for all the tested beetles. C. ferrugineus had the lowest SMh, CCT, and TMmin temperatures, whereas S. zeamais had the highest values of these determined temperatures. C. ferrugineus under a faster stepped-decrease of temperature had higher SMh, CCT, and TMmin temperatures than that under a slower stepped-decrease of temperature, while adults of T. castaneum were not influenced by the temperature decrease rate. The two species of Sitophilus did not survive to the end of the experiment at the faster stepped-decrease of temperature. Two grain moisture contents did not affect these determined temperatures for all tested species.
Smek1/2 is a nuclear chaperone and cofactor for cleaved Wnt receptor Ryk, regulating cortical neurogenesis

Significance Receptor-like tyrosine kinase (Ryk) is a Wnt receptor and is important for many developmental processes, including cranial facial development, neurogenesis, and axon guidance. However, little is known about the role of the intracellular domain, Ryk-ICD, in signal transduction. Its downstream targets are also unknown. We have previously shown that Ryk-ICD is located in the cytoplasm of neural stem cells whereas it moves into the nucleus upon neuronal differentiation. In this study, we discovered that Smek1/2 function as a chaperone for Ryk-ICD during its nuclear localization and that both Smek and Ryk-ICD associate with chromatin to regulate the transcription of downstream target genes and neural differentiation. The receptor-like tyrosine kinase (Ryk), a Wnt receptor, is important for cell fate determination during corticogenesis. During neuronal differentiation, the Ryk intracellular domain (ICD) is cleaved. Cleavage of Ryk and nuclear translocation of Ryk-ICD are required for neuronal differentiation. However, the mechanism of translocation and how it regulates neuronal differentiation remain unclear. Here, we identified Smek1 and Smek2 as Ryk-ICD partners that regulate its nuclear localization and function together with Ryk-ICD in the nucleus through chromatin recruitment and gene transcription regulation. Smek1/2 double knockout mice displayed pronounced defects in the production of cortical neurons, especially interneurons, while the neural stem cell population increased. In addition, both Smek and Ryk-ICD bound to the Dlx1/2 intergenic regulator element and were involved in its transcriptional regulation. These findings demonstrate a mechanism of the Ryk signaling pathway in which Smek1/2 and Ryk-ICD work together to mediate neural cell fate during corticogenesis.
Response to tryptophan of laying hens fed practical diets varying in protein concentration.

Four experiments were conducted with White Leghorn laying hens to estimate their requirement for tryptophan for optimal egg production and other parameters. In the first two experiments, the hens were fed a 14.5% protein diet supplemented with 0, . 025, . 05 and . 075% L-tryptophan. The first experiment was conducted for 12 wk and the second for 55 wk. In the third and fourth experiments, the influence of protein concentration on tryptophan requirement was investigated. Diets formulated to contain 14, 16, and 18% protein were supplemented with 0, . 02, . 04, . 06, or . 08% L-tryptophan. Protein concentration in Experiment 3 was increased by increasing only soybean meal; in Experiment 4, it was increased by increasing all protein concentrates, resulting in the same ratio of tryptophan to protein. These experiments were conducted for 6 wk. Rate of egg production was significantly improved by tryptophan supplementation in Experiments 1 and 2, but production was inferior to that expected for commercial laying hens. The estimated tryptophan requirements were . 137% of the diet and 123 mg/day per hen in Experiment 1 and . 118% of the diet and 95 mg/day per hen in Experiment 2. Egg production was significantly increased by adding tryptophan to the 14% protein diet in Experiment 3 but not to the higher protein diets. The estimated requirement was . 164% of the diet and 168 mg/day per hen. In Experiment 4, tryptophan supplementation significantly increased egg production at all protein percentages, and the requirement increased as the protein increased. Egg weight was not significantly affected by tryptophan supplementation in any of the four experiments. Hepatic lipid accumulation was generally not decreased by tryptophan supplementation.
Cadmium and the laying hen: apparent absorption, tissue distribution and virtual absence of transfer into eggs.

After being given a single oral dose of 40 muCi. of 109CdCl2, laying hens were fed a practical type ration to which 0 or 60 p.p.m. cadmium (Cd, as CdCl2) was added. On the basis of 109Cd in excrement, apparent absorption of the isotope averaged less than 10% of the dose for both diets. Less than 4% of the dose was retained in total body tissue 23 days after dosing. Dietary Cd level did not significantly influence excretion of 109Cd by hens, but hens fed 60 p.p.m. Cd retained a significantly higher proportion of 109Cd dose in liver, kidneys and whole body than did control hens. 109Cd was only detected in blood 48 hours after dosing and more than 75% of radioactivity in the blood occurred in plasma. Hens fed 60 p.p.m. Cd consumed less feed and produced less eggs than control hens. 109Cd was found infrequently at very low levels in yolks of eggs produced by hens fed 60 p.p.m. Cd. No radioactivity was detected in any egg whites, or in yolks of eggs produced by control hens.
Factors Affecting Perceptual Threshold in Argus II Retinal Prosthesis Subjects.

PURPOSE The Argus II epiretinal prosthesis has been developed to provide partial restoration of vision to subjects blinded from outer retinal degenerative disease. Participants were surgically implanted with the system in the United States and Europe in a single arm, prospective, multicenter clinical trial. The purpose of this investigation was to determine which factors affect electrical thresholds in order to inform surgical placement of the device. METHODS Electrode-retina and electrode-fovea distances were determined using SD-OCT and fundus photography, respectively. Perceptual threshold to electrical stimulation of electrodes was measured using custom developed software, in which current amplitude was varied until the threshold was found. Full field stimulus light threshold was measured using the Espion D-FST test. Relationships between electrical threshold and these three explanatory variables (electrode-retina distance, electrode-fovea distance, and monocular light threshold) were quantified using regression. RESULTS Regression analysis showed a significant correlation between electrical threshold and electrode-retina distance (R2 = 0.50, P = 0.0002; n = 703 electrodes). 90.3% of electrodes in contact with the macula (n = 207) elicited percepts at charge densities less than 1 mC/cm2/phase. These threshold data also correlated well with ganglion cell density profile (P = 0.03). A weaker, but still significant, inverse correlation was found between light threshold and electrical threshold (R2 < 0.52, P = 0.01). Multivariate modeling indicated that electrode-retina distance and light threshold are highly predictive of electrode threshold (R2 = 0.87; P < 0.0005). CONCLUSIONS Taken together, these results suggest that while light threshold should be used to inform patient selection, macular contact of the array is paramount. TRANSLATIONAL RELEVANCE Reported Argus II clinical study results are in good agreement with prior in vitro and in vivo studies, and support the development of higher-density systems that employ smaller diameter electrodes. (clinicaltrials.gov identifier: NCT00407602).
Chronic inflammation is a feature of Achilles tendinopathy and rupture

Background Recent investigation of human tissue and cells from positional tendons such as the rotator cuff has clarified the importance of inflammation in the development and progression of tendon disease. These mechanisms remain poorly understood in disease of energy-storing tendons such as the Achilles. Using tissue biopsies from patients, we investigated if inflammation is a feature of Achilles tendinopathy and rupture. Methods We studied Achilles tendon biopsies from symptomatic patients with either mid-portion tendinopathy or rupture for evidence of abnormal inflammatory signatures. Tendon-derived stromal cells from healthy hamstring and diseased Achilles were cultured to determine the effects of cytokine treatment on expression of inflammatory markers. Results Tendinopathic and ruptured Achilles highly expressed CD14+ and CD68+ cells and showed a complex inflammation signature, involving NF-κB, interferon and STAT-6 activation pathways. Interferon markers IRF1 and IRF5 were highly expressed in tendinopathic samples. Achilles ruptures showed increased PTGS2 and interleukin-8 expression. Tendinopathic and ruptured Achilles tissues expressed stromal fibroblast activation markers podoplanin and CD106. Tendon cells isolated from diseased Achilles showed increased expression of pro-inflammatory and stromal fibroblast activation markers after cytokine stimulation compared with healthy hamstring tendon cells. Conclusions Tissue and cells derived from tendinopathic and ruptured Achilles tendons show evidence of chronic (non-resolving) inflammation. The energy-storing Achilles shares common cellular and molecular inflammatory mechanisms with functionally distinct rotator cuff positional tendons. Differences seen in the profile of ruptured Achilles are likely to be attributable to a superimposed phase of acute inflammation and neo-vascularisation. Strategies that target chronic inflammation are of potential therapeutic benefit for patients with Achilles tendon disease.
Fluorescence Recovery Allows the Implementation of a Fluorescence Reporter Gene Platform Applicable for the Detection and Quantification of Horizontal Gene Transfer in Anoxic Environments

ABSTRACT The study of horizontal gene transfer (HGT) in microbial communities has been revolutionized by significant advances in cultivation-independent methods based on fluorescence reporter gene technologies. Recently, the combination of these novel approaches with flow cytometry has presented itself as one of the most powerful tools to study the spread of mobile genetic elements (MGEs) in the environment. However, the use of fluorescent markers, like green fluorescent protein (GFP) and mCherry, is limited by environmental constraints, such as oxygen availability and pH levels, that affect the correct maturation of their fluorophores. Few studies have characterized the effects of such environmental conditions in a systematic way, and the sheer amount of distinct protein variants requires each system to be examined in an individual fashion. The lack of efficient and reliable markers to monitor HGT in anaerobic environments, coupled to the abundance of ecologically and clinically relevant oxygen-deprived niches in which bacteria thrive, calls for the urgent development of suitable tools that permit its study. In an attempt to devise a process that allows the implementation of the mentioned dual-labeling system to anoxic milieus, the aerobic fluorescence recovery of mCherry and GFPmut3, as well as the effect of pH on their fluorescence intensities, was studied. The findings present a solution to an intrinsic problem that has long hampered the utilization of this system, highlight its pH limitations, and provide experimental tools that will help broaden its horizon of application to other fields. IMPORTANCE Many anaerobic environments, like the gastrointestinal tract, anaerobic digesters, and the interiors of dense biofilms, have been shown to be hotspots for horizontal gene transfer (HGT). Despite the increasing wealth of reports warning about the alarming spread of antibiotic resistance determinants, to date, HGT studies mainly rely on cultivation-based methods. Unfortunately, the relevance of these studies is often questionable, as only a minor fraction of bacteria can be cultivated. A recently developed approach to monitoring the fate of plasmids in microbial communities is based on a fluorescence dual-labeling system and allows the bypassing of cultivation. However, the fluorescent proteins on which it is founded are constrained by pH levels and by their strict dependence on oxygen for the maturation of their fluorophores. This study focused on the development and validation of an appropriate aerobic fluorescence recovery (AFR) method for this platform, as this embodies the missing technical link impeding its implementation in anoxic environments.
Zymosan-Induced Peritonitis: Effects on Cardiac Function, Temperature Regulation, Translocation of Bacteria, and Role of Dectin-1

ABSTRACT Zymosan-induced peritonitis is a model commonly used to study systemic inflammatory response syndrome and multiple organ dysfunction syndrome. However, effects of zymosan on cardiac function have not been reported. We evaluated cardiac responses to zymosan in mice and the role of &bgr;-glucan and dectin-1 in mediating these responses. Temperature and cardiac function were evaluated before and after intraperitoneal (i.p.) injection of zymosan (100 or 500 mg/kg) or saline. Chronotropic and dromotropic functions were measured using electrocardiograms (ECGs) collected from conscious mice. Cardiac inotropic function was determined by echocardiography. High-dose zymosan caused a rapid and maintained hypothermia along with visual signs of illness. Baseline heart rate (HR) was unaffected but HR variability (HRV) increased, and there was a modest slowing of ventricular conduction. High-dose zymosan also caused prominent decreases in cardiac contractility at 4 and 24 h. Because zymosan is known to cause gastrointestinal tract pathology, peritoneal wash and blood samples were evaluated for bacteria at 24 h after zymosan or saline injection. Translocation of bacterial occurred in all zymosan-treated mice (n = 3), and two had bacteremia. Purified &bgr;-glucan (50 and 125 mg/kg, i.p.) had no effect on temperature or ECG parameters. However, deletion of dectin-1 modified the ECG responses to high-dose zymosan; slowing of ventricular conduction and the increase in HRV were eliminated but a marked bradycardia appeared at 24 h after zymosan treatment. Zymosan-treated dectin-1 knockout mice also showed hypothermia and visual signs of illness. Fecal samples from dectin-1 knockout mice contained more bacteria than wild types, but zymosan caused less translocation of bacteria. Collectively, these findings demonstrate that zymosan-induced systemic inflammation causes cardiac dysfunction in mice. The data suggest that dectin-1-dependent and -independent mechanisms are involved. Although zymosan treatment causes translocation of bacteria, this effect does not have a major role in the overall systemic response to zymosan.