Miracle-dz/UniFAR-FTUs huggingface dataset:
Investigative MR Cholangiopancreatography for Primary Sclerosing Cholangitis–type Lesions in Children With IBD

Objectives: The aim of the study was to estimate the frequency of primary sclerosing cholangitis (PSC)–type lesions in children with inflammatory bowel disease (IBD) by means of magnetic resonance cholangiopancreatography (MRCP), and to investigate the association between a series of easily applicable data on the one hand and the presentation of such lesions at MRCP on the other hand. Methods: Collected demographic, laboratory, and magnetic resonance enterography data from the records of 73 children with IBD were cross-sectionally related to the MRCP-based diagnosis. Results: Around the time of MRCP, the distribution of IBD subtypes was 64.4%, 24.7%, and 11% for Crohn disease, indeterminate colitis, and ulcerative colitis, respectively. A total of 11 patients (15.1%) were identified with PSC-type lesions. Demographic and magnetic resonance enterography data were unrelated to the MRCP outcome. Biochemical abnormalities were of low prevalence (<50%) among patients with PSC. The abnormality prevalences of aspartate transaminase, alanine transaminase, and &ggr;-glutamyl transferase were significantly higher in the PSC group, both at initial diagnosis of IBD and at the time of MRCP. Less-consistent results were documented for bilirubin and alkaline phosphatase, especially at initial diagnosis of IBD. Conclusions: The abnormality prevalences of aspartate transaminase, alanine transaminase, and &ggr;-glutamyl transferase were significantly higher in the PSC group. Nevertheless, PSC-type lesions frequently occur in pediatric IBD, even if the biochemical profile is hardly indicative of this probability.
Pathogenic VCP/TER94 Alleles Are Dominant Actives and Contribute to Neurodegeneration by Altering Cellular ATP Level in a Drosophila IBMPFD Model

Inclusion body myopathy with Paget's disease of bone and frontotemporal dementia (IBMPFD) is caused by mutations in Valosin-containing protein (VCP), a hexameric AAA ATPase that participates in a variety of cellular processes such as protein degradation, organelle biogenesis, and cell-cycle regulation. To understand how VCP mutations cause IBMPFD, we have established a Drosophila model by overexpressing TER94 (the sole Drosophila VCP ortholog) carrying mutations analogous to those implicated in IBMPFD. Expression of these TER94 mutants in muscle and nervous systems causes tissue degeneration, recapitulating the pathogenic phenotypes in IBMPFD patients. TER94-induced neurodegenerative defects are enhanced by elevated expression of wild-type TER94, suggesting that the pathogenic alleles are dominant active mutations. This conclusion is further supported by the observation that TER94-induced neurodegenerative defects require the formation of hexamer complex, a prerequisite for a functional AAA ATPase. Surprisingly, while disruptions of the ubiquitin-proteasome system (UPS) and the ER–associated degradation (ERAD) have been implicated as causes for VCP–induced tissue degeneration, these processes are not significantly affected in our fly model. Instead, the neurodegenerative defect of TER94 mutants seems sensitive to the level of cellular ATP. We show that increasing cellular ATP by independent mechanisms could suppress the phenotypes of TER94 mutants. Conversely, decreasing cellular ATP would enhance the TER94 mutant phenotypes. Taken together, our analyses have defined the nature of IBMPFD–causing VCP mutations and made an unexpected link between cellular ATP level and IBMPFD pathogenesis.
LRRK2 functions as a Wnt signaling scaffold, bridging cytosolic proteins and membrane-localized LRP6

Mutations in PARK8, encoding leucine-rich repeat kinase 2 (LRRK2), are a frequent cause of Parkinson's disease (PD). Nonetheless, the physiological role of LRRK2 remains unclear. Here, we demonstrate that LRRK2 participates in canonical Wnt signaling as a scaffold. LRRK2 interacts with key Wnt signaling proteins of the β-catenin destruction complex and dishevelled proteins in vivo and is recruited to membranes following Wnt stimulation, where it binds to the Wnt co-receptor low-density lipoprotein receptor-related protein 6 (LRP6) in cellular models. LRRK2, therefore, bridges membrane and cytosolic components of Wnt signaling. Changes in LRRK2 expression affects pathway activity, while pathogenic LRRK2 mutants reduce both signal strength and the LRRK2–LRP6 interaction. Thus, decreased LRRK2-mediated Wnt signaling caused by reduced binding to LRP6 may underlie the neurodegeneration observed in PD. Finally, a newly developed LRRK2 kinase inhibitor disrupted Wnt signaling to a similar extent as pathogenic LRRK2 mutations. The use of LRRK2 kinase inhibition to treat PD may therefore need reconsideration.
Universal Memory Mechanism for Familiarity Recognition and Identification

Macaque monkeys were tested on a delayed-match-to-multiple-sample task, with either a limited set of well trained images (in randomized sequence) or with never-before-seen images. They performed much better with novel images. False positives were mostly limited to catch-trial image repetitions from the preceding trial. This result implies extremely effective one-shot learning, resembling Standing's finding that people detect familiarity for 10,000 once-seen pictures (with 80% accuracy) (Standing, 1973). Familiarity memory may differ essentially from identification, which embeds and generates contextual information. When encountering another person, we can say immediately whether his or her face is familiar. However, it may be difficult for us to identify the same person. To accompany the psychophysical findings, we present a generic neural network model reproducing these behaviors, based on the same conservative Hebbian synaptic plasticity that generates delay activity identification memory. Familiarity becomes the first step toward establishing identification. Adding an inter-trial reset mechanism limits false positives for previous-trial images. The model, unlike previous proposals, relates repetition–recognition with enhanced neural activity, as recently observed experimentally in 92% of differential cells in prefrontal cortex, an area directly involved in familiarity recognition. There may be an essential functional difference between enhanced responses to novel versus to familiar images: The maximal signal from temporal cortex is for novel stimuli, facilitating additional sensory processing of newly acquired stimuli. The maximal signal for familiar stimuli arising in prefrontal cortex facilitates the formation of selective delay activity, as well as additional consolidation of the memory of the image in an upstream cortical module.
Octulose: a forgotten metabolite?

The monosaccharide octulose was first isolated and identified about seventy years ago. Although this sugar has frequently been found in plants, bacteria, yeast and animals, its metabolic function has hardly been explored. It often occurs in small amounts, but occasionally it is highly abundant, notably in some resurrection plants. Recent results show that its synthesis may involve an alternative pentose phosphate pathway and that when present in large amounts it might confer important benefits such as ROS scavenging. It could also have value for nutrition and healthcare. The time is ripe for developing our understanding further.
Predifferentiated GABAergic Neural Precursor Transplants for Alleviation of Dysesthetic Central Pain Following Excitotoxic Spinal Cord Injury

Intraspinal quisqualic acid (QUIS) injury induce (i) mechanical and thermal hyperalgesia, (ii) progressive self-injurious overgrooming of the affected dermatome. The latter is thought to resemble painful dysesthesia observed in spinal cord injury (SCI) patients. We have reported previously loss of endogenous GABA immunoreactive (IR) cells in the superficial dorsal horn of QUIS rats 2 weeks post injury. Further histological evaluation showed that GABA-, glycine-, and synaptic vesicular transporter VIAAT-IR persisted but were substantially decreased in the injured spinal cord. In this study, partially differentiated GABA-IR embryonic neural precursor cells (NPCs) were transplanted into the spinal cord of QUIS rats to reverse overgrooming by replenishing lost inhibitory circuitry. Rat E14 NPCs were predifferentiated in 0.1 ng/ml FGF-2 for 4 h prior to transplantation. In vitro immunocytochemistry of transplant cohort showed large population of GABA-IR NPCs that double labeled with nestin but few colocalized with NeuN, indicating partial maturation. Two weeks following QUIS lesion at T12-L1, and following the onset of overgrooming, NPCs were transplanted into the QUIS lesion sites; bovine adrenal fibroblast cells were used as control. Overgrooming was reduced in >55.5% of NPC grafted animals, with inverse relationship between the number of surviving GABA-IR cells and the size of overgrooming. Fibroblast-control animals showed a progressive worsening of overgrooming. At 3 weeks post-transplantation, numerous GABA-, nestin-, and GFAP-IR cells were present in the lesion site. Surviving grafted GABA-IR NPCs were NeuN+ and GFAP−. These results indicate that partially differentiated NPCs survive and differentiate in vivo into neuronal cells following transplantation into an injured spinal cord. GABA-IR NPC transplants can restore lost dorsal horn inhibitory signaling and are useful in alleviating central pain following SCI.
Matrix metalloproteinase-1 expression in breast carcinoma: a marker for unfavorable prognosis

Matrix metalloproteinase-1 (MMP1) is a member of the matrix metalloproteinases family, and its aberrant expression is implicated in tumor invasion and metastasis. However, the relationship between MMP1 abnormal expression and clinical outcome in breast cancer patients remains to be elucidated. To address this issue, we conducted immunohistochemistry in breast cancer and adjacent normal tissues, and mined the transcriptional and survival data of MMP1 in breast cancer patients through Oncomine, Kaplan-Meier Plotter, bc-GenExMiner, COSMIC and cBioPortal databases. First, we found that both protein and mRNA levels of MMP1 expression were significantly higher in breast cancer tissues. Second, high MMP1 mRNA expression correlated with worse overall survival among grade II (HR = 1.75; p = 0.011), nodal-negative (HR = 2.00; p = 0.00028), ER-positive (HR = 1.61; p = 0.00027) and HER2-negative (HR = 3.17; p = 0.029) patients with breast cancer by using Kaplan-Meier plotter database. Third, the overexpression of MMP1 was associated with unfavorable survival results including overall survival (HR = 1.6; p = 1.6e-05), relapse free survival (HR = 1.78; p < 1e-16) and distant metastasis free survival (HR = 1.65; p = 5.3e-05) in patients with breast cancer. Taken together, the expression status of MMP1 is a significant prognostic indicator and a potential drug target for breast cancer.
Institutional Investors and Stock Prices: Destabilizing and Stabilizing Herds

From 1980 to 2005, institutional trading destabilizes stock prices. Specifically, stocks with herds of institutional buying in a given quarter suer price declines of nearly three percent from four to eight quarters after the herding. Moreover, institutions do not suer losses from the destabilization; they exit before prices reverse. These results extend the “riding the bubble” findings of Brunnermeier and Nagel (2004) beyond just hedge funds’ trading of technology stocks in the 1990s. Evidence that institutions are aware of the overpricings of the stocks they enter extends across time, across stocks, and across institutions. We also find that the entry buys of institutions are the drivers of the destabilization, while sell herds do not destabilize. In fact, exit sells actually stabilize prices. In other words, entries tend to push prices above their intrinsic levels while exits tend to push prices toward their correct levels. However, on net, the destabilization eect of institutional trading dominates.
Vertebral Bomb Radiocarbon Suggests Extreme Longevity in White Sharks

Conservation and management efforts for white sharks (Carcharodon carcharias) remain hampered by a lack of basic demographic information including age and growth rates. Sharks are typically aged by counting growth bands sequentially deposited in their vertebrae, but the assumption of annual deposition of these band pairs requires testing. We compared radiocarbon (Δ14C) values in vertebrae from four female and four male white sharks from the northwestern Atlantic Ocean (NWA) with reference chronologies documenting the marine uptake of 14C produced by atmospheric testing of thermonuclear devices to generate the first radiocarbon age estimates for adult white sharks. Age estimates were up to 40 years old for the largest female (fork length [FL]: 526 cm) and 73 years old for the largest male (FL: 493 cm). Our results dramatically extend the maximum age and longevity of white sharks compared to earlier studies, hint at possible sexual dimorphism in growth rates, and raise concerns that white shark populations are considerably more sensitive to human-induced mortality than previously thought.
High frequency diaphragmatic fatigue detected with paired stimuli in humans.

PURPOSE The purpose of this study was to determine whether high frequency fatigue was present in the diaphragm after intense whole body endurance exercise. METHODS We used bilateral phrenic nerve stimulation (BPNS) before and during recovery from whole body exercise to detect fatigue in the diaphragm. To detect high frequency fatigue we used paired stimuli at 10, 20, 50, 70, and 100 Hz frequency and determined the transdiaphragmatic pressure (Pdi) response to the second stimulation (T2). RESULTS The subjects (N = 10) exercised at 93.3 +/- 2.3% of their VO2max for 9.9 +/- 0.5 min. The Pdi response to "twitch" and 10 Hz "tetanic" stimulation was decreased immediately after exercise versus pre-exercise values (-23.4 +/- 3.3%). The T2 amplitude was substantially reduced at all frequencies immediately after exercise (-28.0%), but by 30 min into recovery the T2 amplitude at 70 and 100 Hz was not different from pre-exercise values. In contrast, at 10 and 20 Hz the T2 response was still significantly reduced. CONCLUSIONS We interpret these data to mean that high frequency fatigue as well as low frequency fatigue were present in the diaphragm after intense whole body endurance exercise.
Perspectives on artificial intelligence planning

Planning is a key area in Artificial Intelligence. In its general form, planning is concerned with the automatic synthesis of action strategies (plans) from a description of actions, sensors, and goals. Planning thus contrasts with two other approaches to intelligent behavior: the programming approach, where action strategies are defined by hand, and the learning approach, where action strategies are inferred from experience. Different assumptions about the nature of actions, sensors, and costs lead to various forms of planning: planning with complete information and deterministic actions (classical planning), planning with non-deterministic actions and sensing, planning with temporal and concurrent actions, etc. Most work so far has been devoted to classical planning, where significant changes have taken place in the last few years. On the methodological side, the area has become more empirical, on the technical side, approaches based on heuristic or constrained-based search have become common.In this paper, I try to provide a coherent picture of Planning in AI, making emphasis on the mathematical models that underlie various forms of planning and the ideas that have been found most useful computationally.
The Yeast Dynamin-like Protein, Mgm1p, Functions on the Mitochondrial Outer Membrane to Mediate Mitochondrial Inheritance

The mdm17 mutation causes temperature-dependent defects in mitochondrial inheritance, mitochondrial morphology, and the maintenance of mitochondrial DNA in the yeast Saccharomyces cerevisiae. Defects in mitochondrial transmission to daughter buds and changes in mitochondrial morphology were apparent within 30 min after shifting cells to 37°C, while loss of the mitochondrial genome occurred after 4–24 h at the elevated temperature. The mdm17 lesion mapped to MGM1, a gene encoding a dynamin-like GTPase previously implicated in mitochondrial genome maintenance, and the cloned MGM1 gene complements all of the mdm17 mutant phenotypes. Cells with an mgm1-null mutation displayed aberrant mitochondrial inheritance and morphology. A version of mgm1 mutated in a conserved residue in the putative GTP-binding site was unable to complement any of the mutant defects. It also caused aberrant mitochondrial distribution and morphology when expressed at high levels in cells that also contained a wild-type copy of the gene. Mgm1p was localized to the mitochondrial outer membrane and fractionated as a component of a high molecular weight complex. These results indicate that Mgm1p is a mitochondrial inheritance and morphology component that functions on the mitochondrial surface.
Development and Evaluation of a Device for Presenting Tactile Stimuli

We are especially interested in the human ability to recognize shape using the delayed matching paradigm in active and passive touch studies. To investigate the characteristics of shape recognition, stimulus presentation control is very important because a subtle difference in the stimulus presentation will influence the results. In this study, we propose a new device that precisely controls the stimulus presentation and performs psychobehavioral measurements in haptics studies. And we also conducted an active/passive shape discrimination experiment to evaluate the performance of the device. Twenty right-handed students consented to participate in the experiment. The results suggest that the device might serve as a comprehensive haptic device that allows different types of haptic stimuli to be presented precisely to subjects to measure various psychobehavioral parameters.
Predicting the Micro-Timing of User Input for an Incremental Spoken Dialogue System that Completes a User’s Ongoing Turn

We present the novel task of predicting temporal features of continuations of user input, while that input is still ongoing. We show that the remaining duration of an ongoing word, as well as the duration of the next can be predicted reasonably well, and we put this information to use in a system that synchronously completes a user's speech. While we focus on collaborative completions, the techniques presented here may also be useful for the alignment of back-channels and immediate turn-taking in an incremental SDS, or to synchronously monitor the user's speech fluency for other reasons.
Effects of monomer compositions on physicochemical properties of composite resins

Abstract The aim of this study was to evaluate the cohesive strength (CS), surface roughness (Ra), and weight loss (WL) of different composite resins. Three composite resins (Filtek Z100; Filtek Z350; Filtek P90, 3M ESPE) were tested. To evaluate CS, an hourglass silicone mold (11 × 2 × 1 mm) was used (n = 10). The Ra and WL tests were performed using a circular mold (5 × 2 mm, n = 10). The composite resins were light-cured with an LED light curing device (FreeLight 2, 3M ESPE) for 40 s and 1000 mW/cm2. The CS test was performed using a universal testing machine (Instron 4411, Instron) at a crosshead speed of 0.5 mm/min and cell load of 500 N. The initial mass weight was registered (analytical digital balance) and the initial Ra reading evaluated using a profilometer (Surftest 211, Mitutoyo). The specimens were submitted to 30,000 brushing cycles. The WL and the final Ra were evaluated. All data were subjected to one-way ANOVA, followed by Tukey’s test (p < 0.05). Filtek Z100 showed the highest values of Ra and Filtek Z350 the lowest values of Ra. When considering CS, Filtek Z350 and Z100 had the highest mean values. Filtek P90 had the highest mean value of WL. The organic matrix and the type, shape, and size of fillers may influence the physicochemical properties of composite resins.
Corrosion of an Advanced Al-Cu-Li Alloy for Aerospace Applications

This paper discusses two Al-Cu alloys for aerospace applications, one which has a high concentration (>1.8 wt.%) of Li. These alloys are AA2024-T3 (Al-Cu) and AA2099-T8E77 (Al-Cu-Li) and are both in the plate format. Anodic polarisation and immersion in a 3.5 wt. % NaCl solution have been carried out and a comparison of the corrosion mechanisms have been made. Both alloys showed extensive corrosion over the surface, AA2024-T3, however, had areas of pitting that had joined together forming large corrosion regions, whereas AA2099-T8E77 had numerous corrosion pits that had not merged. The pits on AA2099-T8E77 propagated to a depth ~120 µm whereas on AA2024-T3 the maximum depth was ~85 µm. Intergranular and transgranular corrosion was also observed on the AA2024-T3 alloy following anodic polarisation. AA2099-T8E77 had reduced corrosion resistance with regards to Epit-Ecorr values. For both alloys, dissolution of matrix material surrounding the Cu-rich intermetallic particles was observed, highlighting the particles’ cathodic nature.
Ambient noise imaging in warm shallow waters; robust statistical algorithms and range estimation.

The high frequency ambient noise in warm shallow waters is dominated by snapping shrimp. The loud snapping noises they produce are impulsive and broadband. As the noise propagates through the water, it interacts with the seabed, sea surface, and submerged objects. An array of acoustic pressure sensors can produce images of the submerged objects using this noise as the source of acoustic "illumination. " This concept is called ambient noise imaging (ANI) and was demonstrated using ADONIS, an ANI camera developed at the Scripps Institution of Oceanography. To overcome some of the limitations of ADONIS, a second generation ANI camera (ROMANIS) was developed at the National University of Singapore. The acoustic time series recordings made by ROMANIS during field experiments in Singapore show that the ambient noise is well modeled by a symmetric α-stable (SαS) distribution. As high-order moments of SαS distributions generally do not converge, ANI algorithms based on low-order moments and fractiles are developed and demonstrated. By localizing nearby snaps and identifying the echoes from an object, the range to the object can be passively estimated. This technique is also demonstrated using the data collected with ROMANIS.
A Biventricular ICD System with Biventricular Defibrillation

We describe the case of a 59‐year‐old gentleman with severe dilated cardiomyopathy requiring implantation of a dual‐chamber biventricular implantable cardioverter‐defibrillator (ICD). High defibrillation thresholds (DFT) were encountered at implant with an inadequate defibrillation safety margin. Testing of all possible shock vectors/polarities with and without the SVC coil and optimization of the distal RV coil position all proved inadequate. A satisfactory defibrillation safety margin was achieved following placement of a second lead in the coronary sinus to enable biventricular defibrillation. This case highlights an additional strategy for combating high DFTs and is an option even in dual‐chamber biventricular ICD systems.
Preferential Regular Path Queries

In this paper, we introduce preferential regular path queries. These are regular path queries whose symbols are annotated with preference weights for "scaling" up or down the intrinsic importance of matching a symbol against a (semistructured) database edge label. Annotated regular path queries are expressed syntactically as annotated regular expressions. We interpret these expressions in a uniform semiring framework, which allows different semantic interpretations for the same syntactic annotations. For our preference queries, we study three important aspects: (1) (progressive) query answering (2) (certain) query answering in LAV data-integration systems, and (3) query containment and equivalence. In all of these, we obtain important positive results, which encourage the use of our preference framework for enhanced querying of semistructured databases.