Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional Effect of Pim1 Depends upon Intracellular Localization in Human Cardiac Progenitor Cells

Background: Age and disease affect cardiac expression and localization of Pim1. Results: Survival and proliferation are enhanced and senescence is antagonized by intracellular targeting of Pim1. Conclusion: Cardioprotective properties are emphasized by targeting Pim1 expression in human cardiac progenitor cells. Significance: Compartmentalizing Pim1 to enhance stem cell characteristics can be used for targeted molecular intervention to improve cell-based regenerative therapy. Human cardiac progenitor cells (hCPC) improve heart function after autologous transfer in heart failure patients. Regenerative potential of hCPCs is severely limited with age, requiring genetic modification to enhance therapeutic potential. A legacy of work from our laboratory with Pim1 kinase reveals effects on proliferation, survival, metabolism, and rejuvenation of hCPCs in vitro and in vivo. We demonstrate that subcellular targeting of Pim1 bolsters the distinct cardioprotective effects of this kinase in hCPCs to increase proliferation and survival, and antagonize cellular senescence. Adult hCPCs isolated from patients undergoing left ventricular assist device implantation were engineered to overexpress Pim1 throughout the cell (PimWT) or targeted to either mitochondrial (Mito-Pim1) or nuclear (Nuc-Pim1) compartments. Nuc-Pim1 enhances stem cell youthfulness associated with decreased senescence-associated β-galactosidase activity, preserved telomere length, reduced expression of p16 and p53, and up-regulation of nucleostemin relative to PimWT hCPCs. Alternately, Mito-Pim1 enhances survival by increasing expression of Bcl-2 and Bcl-XL and decreasing cell death after H2O2 treatment, thereby preserving mitochondrial integrity superior to PimWT. Mito-Pim1 increases the proliferation rate by up-regulation of cell cycle modulators Cyclin D, CDK4, and phospho-Rb. Optimal stem cell traits such as proliferation, survival, and increased youthful properties of aged hCPCs are enhanced after targeted Pim1 localization to mitochondrial or nuclear compartments. Targeted Pim1 overexpression in hCPCs allows for selection of the desired phenotypic properties to overcome patient variability and improve specific stem cell characteristics.
LiFS: An Attribute-Rich File System for Storage Class Memories

As the number and variety of files stored and accessed by a typical user has dramatically increased, existing file system structures have begun to fail as a mechanism for managing all of the information contained in those files. Many applications—email clients, multimedia management applications, and desktop search engines are examples— have been forced to develop their own richer metadata infrastructures. While effective, these solutions are generally non-standard, non-portable, non-sharable across applications, users or platforms, proprietary, and potentially inefficient. In the interest of providing a rich, efficient, shared file system metadata infrastructure, we have developed the Linking File System (LiFS). Taking advantage of non-volatile storage class memories, LiFS supports a wide variety of user and application metadata needs while efficiently supporting traditional file system operations.
Preventing Mitochondrial Fission Impairs Mitochondrial Function and Leads to Loss of Mitochondrial DNA

Mitochondria form a highly dynamic tubular network, the morphology of which is regulated by frequent fission and fusion events. However, the role of mitochondrial fission in homeostasis of the organelle is still unknown. Here we report that preventing mitochondrial fission, by down-regulating expression of Drp1 in mammalian cells leads to a loss of mitochondrial DNA and a decrease of mitochondrial respiration coupled to an increase in the levels of cellular reactive oxygen species (ROS). At the cellular level, mitochondrial dysfunction resulting from the lack of fission leads to a drop in the levels of cellular ATP, an inhibition of cell proliferation and an increase in autophagy. In conclusion, we propose that mitochondrial fission is required for preservation of mitochondrial function and thereby for maintenance of cellular homeostasis.
Hairy cell leukemia 2018 Update on diagnosis, risk-stratification, and treatment

Disease overview: Hairy cell leukemia (HCL) and HCL-like disorders, including HCL variant (HCL-V) and splenic diffuse red pulp lymphoma (SDRPL), are a very heterogeneous group of mature lymphoid B-cell disorders, characterized by the identification of hairy cells, a specific genetic profile, a different clinical course and the need for appropriate treatment. Diagnosis: Diagnosis of HCL is based on morphological evidence of hairy cells, an HCL immunologic score of 3 or 4 based on the CD11C, CD103, CD123, and CD25 expression, the trephine biopsy which makes it possible to specify the degree of tumoral medullary infiltration and the presence of BRAF V600E somatic mutation. Risk stratification: Progression of patients with HCL is based on a large splenomegaly, leukocytosis, a high number of hairy cells in the peripheral blood and the immunoglobulin heavy chain variable region gene mutational status. VH4-34 positive HCL cases are associated with poor prognosis Risk adapted therapy: Purine analogs (PNA) are indicated in symptomatic first line HCL patients. The use of PNA followed by rituximab represents an alternative option. Management of progressive or refractory disease: It is based on the use of BRAF inhibitors associated or not with MEK inhibitors, recombinant immunoconjugates targeting CD22 or BCR
Mining chains of relations

Traditional data mining applications consider the problem of mining a single relation between two attributes. For example, in a scientific bibliography database, authors are related to papers, and we may be interested in discovering association rules between authors. However, in real life, we often have multiple attributes related though chains of relations. For example, authors write papers, and papers concern one or more topics. Mining such relational chains poses additional challenges. In this paper we consider the following problem: given a chain of two relations R/sub 1/ (A, P) and R/sub 2/(P, T) we want to find selectors for the objects in T such that the projected relation between A and P satisfies a specific property. The motivation for our approach is that a given property might not hold on the whole dataset, but it might hold when projecting the data on a selector set. We discuss various algorithms and we examine the conditions under which the a priori technique can be used. We experimentally demonstrate the effectiveness of our methods.
Impact of Langmuir Turbulence on the Thermal Response of the Ocean Surface Mixed Layer to Supertyphoon Haitang (2005)

Langmuir turbulence (LT) due to the Craik–Leibovich vortex force had a clear impact on the thermal response of the ocean mixed layer to Supertyphoon Haitang (2005) east of the Luzon Strait. This impact is investigated using a 3D wave–current coupled framework consisting of the Princeton Ocean Model with the generalized coordinate system (POMgcs) and the Simulating Waves Nearshore (SWAN) wave model. The Coriolis–Stokes forcing (CSF), the Craik–Leibovich vortex forcing (CLVF), and the second-moment closure model of LT developed by Harcourt are introduced into the circulation model. The coupled system is able to reproduce the upper-ocean temperature and surface mixed layer depth reasonably well during the forced stage of the supertyphoon. The typhoon-induced “cold suction” and “heat pump” processes are significantly affected by LT. Local LT mixing strengthened the sea surface cooling by more than 0.5°C in most typhoon-affected regions. Besides LT, Lagrangian advection of temperature also modulates the SST cooling, inducing a negative (positive) SST difference in the vicinity of the typhoon center (outside of the cooling region). In addition, CLVF has the same order of magnitude as the horizontal advection in the typhoon-induced strong-vorticity region. While the geostrophy is broken down during the forced stage of Haitang, CLVF can help establish and maintain typhoon-induced quasigeostrophy during and after the typhoon. Finally, the effect of LT on the countergradient turbulent flux under the supertyphoon is discussed.
Communities of arbuscular mycorrhizal fungi in arable soils are not necessarily low in diversity

Communities of arbuscular mycorrhizal fungi (AMF) in five agricultural field sites of different management intensities were studied. Variable regions of the ribosomal RNA genes were used to detect and identify AMF directly within colonized roots. Roots from a continuous maize monoculture showed low AMF diversity, in agreement with previous reports on molecular diversity of AMF in agricultural soils. In contrast, a substantially higher diversity of AMF was found throughout the long term ‘DOK’ field experiment, where organic and conventional agricultural practices have been compared side by side since 1978. In this experiment, a 7‐year crop rotation is performed under lower levels of inorganic fertilizer input and chemical pest control. These results are in good agreement with analyses of the spore community previously conducted in these field sites. In a third site, an organically managed leek field with soil of very high phosphate content reflecting the highly intensive conventional field history and intensive tillage, we detected a low‐diversity community comparable to the maize monoculture. In addition to fungi from Glomus group A, which have previously been reported to dominate arable soils, we regularly found members of the genera Scutellospora, Paraglomus and Acaulospora. The genus Acaulospora was shown to occur more frequently early in the growing season, suggesting that the life history strategy of AMF may influence the active community at a given time. These data show that the diversity of AMF is not always low in arable soils. Furthermore, low‐input agriculture involving crop rotation may provide better conditions to preserve AMF diversity, by preventing the selection for the few AMF taxa tolerating high nutrient levels.
The SP Theory of Intelligence: Distinctive Features and Advantages

This paper aims to highlight distinctive features of the SP theory of intelligence, realized in the SP computer model, and its apparent advantages compared with some AI-related alternatives. Perhaps most importantly, the theory simplifies and integrates observations and concepts in AI-related areas, and has potential to simplify and integrate of structures and processes in computing systems. Unlike most other AI-related theories, the SP theory is itself a theory of computing, which can be the basis for new architectures for computers. Fundamental in the theory is information compression via the matching and unification of patterns and, more specifically, via a concept of multiple alignment. The theory promotes transparency in the representation and processing of knowledge, and unsupervised learning of natural structures via information compression. It provides an interpretation of aspects of mathematics and an interpretation of phenomena in human perception and cognition. concepts in the theory may be realized in terms of neurons and their inter-connections (SP-neural). These features and advantages of the SP system are discussed in relation to AI-related alternatives: the concept of minimum length encoding and related concepts, how computational and energy efficiency in computing may be achieved, deep learning in neural networks, unified theories of cognition and related research, universal search, Bayesian networks and some other models for AI, IBM's Watson, solving problems associated with big data and in the development of intelligence in autonomous robots, pattern recognition and vision, the learning and processing of natural language, exact and inexact forms of reasoning, representation and processing of diverse forms of knowledge, and software engineering. In conclusion, the SP system can provide a firm foundation for the long-term development of AI and related areas, and at the same time, it may deliver useful results on relatively short timescales.
Pto Kinase Binds Two Domains of AvrPtoB and Its Proximity to the Effector E3 Ligase Determines if It Evades Degradation and Activates Plant Immunity

The tomato—Pseudomonas syringae pv. tomato (Pst)—pathosystem is one of the best understood models for plant-pathogen interactions. Certain wild relatives of tomato express two closely related members of the same kinase family, Pto and Fen, which recognize the Pst virulence protein AvrPtoB and activate effector-triggered immunity (ETI). AvrPtoB, however, contains an E3 ubiquitin ligase domain in its carboxyl terminus which causes degradation of Fen and undermines its ability to activate ETI. In contrast, Pto evades AvrPtoB-mediated degradation and triggers ETI in response to the effector. It has been reported recently that Pto has higher kinase activity than Fen and that this difference allows Pto to inactivate the E3 ligase through phosphorylation of threonine-450 (T450) in AvrPtoB. Here we show that, in contrast to Fen which can only interact with a single domain proximal to the E3 ligase of AvrPtoB, Pto binds two distinct domains of the effector, the same site as Fen and another N-terminal domain. In the absence of E3 ligase activity Pto binds to either domain of AvrPtoB to activate ETI. However, the presence of an active E3 ligase domain causes ubiquitination of Pto that interacts with the domain proximal to the E3 ligase, identical to ubiquitination of Fen. Only when Pto binds its unique distal domain can it resist AvrPtoB-mediated degradation and activate ETI. We show that phosphorylation of T450 is not required for Pto-mediated resistance in vivo and that a kinase-inactive version of Pto is still capable of activating ETI in response to AvrPtoB. Our results demonstrate that the ability of Pto to interact with a second site distal to the E3 ligase domain in AvrPtoB, and not a higher kinase activity or T450 phosphorylation, allows Pto to evade ubiquitination and to confer immunity to Pst.
The Cardioprotective Effect of Mildronate is Diminished After Co-Treatment With l-Carnitine

Mildronate, an inhibitor of l-carnitine biosynthesis and uptake, is a cardioprotective drug whose mechanism of action is thought to rely on the changes in concentration of l-carnitine in heart tissue. In the present study, we compared the cardioprotective effect of mildronate (100 mg/kg) and a combination of mildronate and l-carnitine (100 + 100 mg/kg) administered for 14 days with respect to the observed changes in l-carnitine level and carnitine palmitoyltransferase I (CPT-I)-dependent fatty acid metabolism in the heart tissues. Concentrations of l-carnitine and its precursor γ-butyrobetaine (GBB) were measured by ultraperformance liquid chromatography with tandem mass spectrometry. In addition, mitochondrial respiration, activity of CPT-I, and expression of CPT-IA/B messenger RNA (mRNA) were measured. Isolated rat hearts were subjected to ischemia–reperfusion injury. Administration of mildronate induced a 69% decrease in l-carnitine concentration and a 6-fold increase in GBB concentration in the heart tissue as well as a 27% decrease in CPT-I-dependent mitochondrial respiration on palmitoyl-coenzyme A. In addition, mildronate treatment induced a significant reduction in infarct size and also diminished the ischemia-induced respiration stimulation by exogenous cytochrome c. Treatment with a combination had no significant impact on l-carnitine concentration, CPT-I-dependent mitochondrial respiration, and infarct size. Our results demonstrated that the mildronate-induced decrease in l-carnitine concentration, concomitant decrease in fatty acid transport, and maintenance of the intactness of outer mitochondrial membrane in heart mitochondria are the key mechanisms of action for the anti-infarction activity of mildronate.
Texture modelling with non-contiguous filters

Markov random field models of textures describe images by statistics of local image features and identify conditional dependencies between pixels. To account for higher-order inter-dependencies between multiple pixels, most common high-order modelling follows the well-known FRAME or Fields of Experts (FoE) frameworks in using marginals of the responses of various filters as descriptive statistics. The filters are nearly always square, relatively small, and fixed in number. However, large sparse (non-contiguous) texture-specific filters can model long range and large-scale interactions much more simply and cheaply than large square filters, multiple scales or layers of filters. We learn models with an extension of `model nesting' and merge the FRAME and FoE models, using histograms of the responses of sparse linear filters as sufficient statistics together with marginals of long-range pairwise signal differences (which are linear filters of size 2). We give a simple algorithm for learning both the shapes and coefficients of the sparse linear filters. Nested models are built by adding filters or other features iteratively to a base model to rectify statistical differences from the training data. The models are applied to texture modelling, specifically synthesis and inpainting, which demonstrates their effectiveness.
Linking atmospheric circulation patterns with hydro‐geomorphic disasters in Peru

The occurrence of El Niño has been generally considered the main driver of hydro‐geomorphic processes in Peru. However, the climatic characterization of hydro‐geomorphic events (HGE) occurring in the absence of El Niño remains scarce. Information contained in the DesInventar disaster database suggests a widespread occurrence of HGE associated to cold‐neutral sea surface temperature (SST) in the central Pacific and south tropical Atlantic. Here, we aim at characterizing synoptic patterns associated with HGE that have occurred over last 35 years related to the different El Niño types and focusing as well on the non‐Niño phases. We use the ERA‐Interim reanalysis climate data and implement self‐organizing maps to assess the link between HGE in Peru and specific synoptic patterns. Results suggest that synoptic patterns associated with La Niña and neutral conditions play an important role in the occurrence of hydro‐geomorphic disasters in Peru during the austral summer. A total of 21% of the events are associated only with the 1972–1973, 1982–1983 and 1997–1998 El Niño events and are mainly focused in the northern Pacific coast of the country (i.e., Tumbes, Piura and Lambayeque) while more than 36% of the recorded events in the database were associated with La Niña and neutral conditions between 1970 and 2013. La Niña‐related events were more relevant in the Andean–Amazonian regions, whereas neutral conditions were related to more frequent HGEs in the southern regions (south of the 13.25°S) along the Peruvian Pacific coast. These outcomes imply an enhanced understanding of the synoptic mechanisms leading to the occurrence of HGE and contribute to a better understanding of the triggers of HGE causing disaster no exclusively related to El Niño‐like years in Peru.
Perceived Versus Actual Risk for Hypertension and Diabetes in the African American Community

Hypertension and diabetes mellitus are leading health concerns in the United States. Despite a disproportionate burden of both conditions among African Americans, it is estimated that 44% of diabetes cases and one quarter of hypertension cases within this population are undiagnosed. Lack of awareness of the risk of these conditions may hinder preventive efforts and the adoption of positive lifestyle changes. Based on the findings from a pilot study to develop and standardize uniform screening forms for hypertension and diabetes, this article reports on the perceived risk versus actual risk of developing these conditions among primarily African American participants using a community-based screening tool. Each form assessed both perceived and actual risk of diabetes and hypertension, respectively. A total of 265 hypertension and 225 diabetes screening forms were randomly selected from eight sites across the country. The risk perception of the overall study sample was similar to its actual risk for developing either condition. However, a significant proportion of individuals who scored at high risk for diabetes or hypertension were unaware of their risk for these conditions. These results suggest the need for developing culturally relevant interventions, public health education, and policies that address the risk misperceptions among this group.
Site-Specific Secretome Map Evidences VSMC-Related Markers of Coronary Atherosclerosis Grade and Extent in the Hypercholesterolemic Swine

A major drawback in coronary atherosclerosis (ATS) research is the difficulty of investigating early phase of plaque growth and related features in the clinical context. In this study, secreted proteins from atherosclerotic coronary arteries in a hypercholesterolemic swine model were characterized by a proteomics approach and their expression was correlated to site-specific ATS stage and extent. A wide coronary artery map of secreted proteins has been obtained in high fat (HF) diet induced ATS swine model and a significantly different expression of many proteins related to vascular smooth muscle cell (VSMC) activation/migration has been identified. Significant associations with ATS stage of HF coronary lesions were found for several VSMC-derived proteins and validated for chitinase 3 like protein 1 (CHI3L1) by tissue immunoexpression. A direct correlation (R 2 = 0.85) was evidenced with intima to media thickness ratio values and ELISA confirmed the higher blood concentrations of CHI3L1 in HF cases. These findings confirmed the pivotal role of VSMCs in coronary plaque development and demonstrated a strong site-specific relation between VSMC-secreted CHI3L1 and lesion grade, suggesting that this protein could be proposed as a useful biomarker for diagnosing and staging of atherosclerotic lesions in coronary artery disease.
Pelvic Discontinuity: Modern Techniques and Outcomes for Treating Pelvic Disassociation

Pelvic discontinuity is an uncommon condition that usually presents in the revision total hip arthroplasty population. However, its incidence will most likely increase due to the increasing number of primary and revision total hip arthroplasties (THA) done in recent years. Pelvic discontinuity (acetabular disassociation) is perhaps one of the more challenging cases for the hip arthroplasty surgeon to manage. Historically, the management of pelvic discontinuity has been wrought with many challenges. What follows is a review of the current techniques and outcomes for acetabular reconstruction in patients with acetabular disassociation including: porous metal components, internal fixation with acetabular reconstruction, acetabular distraction with jumbo cups, cup and cage construct, and the use of custom triflange. The complexity of pelvic discontinuity and with the myriad of options available to the hip arthroplasty surgeon to address this particular issue, pre-operative planning becomes all the more essential.
X-ray properties of the transient pulsar 3A 0535+262 in quiescence

We present the timing and spectral properties of the transient Be/X-ray binary pulsar 3A 0535+262 during quiescence using three observations with the narrow field imaging instruments (NFI) of BeppoSAX. Assuming a distance of 2 kpc for this system, the 2-10 keV X-ray luminosities measured from the three observations are in the range of 1.5-4.0 × 10 33 erg s −1 , indicating a very low rate of accretion. We report the detection of pulsations at a very low luminosity of 2 × 10 33 erg s −1 during one of the three observations, though at this accretion rate the system is expected to be in the centrifugally inhibited regime. The X-ray spectra for the unpulsed observations are best modeled as power law type while a combined model of power law and black-body is required to fit the pulsed spectrum.