Miracle-dz/UniFAR-FTUs huggingface dataset:
Liver-specific Loss of Long Chain Acyl-CoA Synthetase-1 Decreases Triacylglycerol Synthesis and β-Oxidation and Alters Phospholipid Fatty Acid Composition*

In mammals, a family of five acyl-CoA synthetases (ACSLs), each the product of a separate gene, activates long chain fatty acids to form acyl-CoAs. Because the ACSL isoforms have overlapping preferences for fatty acid chain length and saturation and are expressed in many of the same tissues, the individual function of each isoform has remained uncertain. Thus, we constructed a mouse model with a liver-specific knock-out of ACSL1, a major ACSL isoform in liver. Eliminating ACSL1 in liver resulted in a 50% decrease in total hepatic ACSL activity and a 25–35% decrease in long chain acyl-CoA content. Although the content of triacylglycerol was unchanged in Acsl1L−/− liver after mice were fed either low or high fat diets, in isolated primary hepatocytes the absence of ACSL1 diminished the incorporation of [14C]oleate into triacylglycerol. Further, small but consistent increases were observed in the percentage of 16:0 in phosphatidylcholine and phosphatidylethanolamine and of 18:1 in phosphatidylethanolamine and lysophosphatidylcholine, whereas concomitant decreases were seen in 18:0 in phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and lysophosphatidylcholine. In addition, decreases in long chain acylcarnitine content and diminished production of acid-soluble metabolites from [14C]oleate suggested that hepatic ACSL1 is important for mitochondrial β-oxidation of long chain fatty acids. Because the Acsl1L−/− mice were not protected from developing either high fat diet-induced hepatic steatosis or insulin resistance, our study suggests that lowering the content of hepatic acyl-CoA without a concomitant decrease in triacylglycerol and other lipid intermediates is insufficient to protect against hepatic insulin resistance.
New Insights into the Methodology of L-Arginine-Induced Acute Pancreatitis

Animal models are ideal to study the pathomechanism and therapy of acute pancreatitis (AP). The use of L-arginine-induced AP model is nowadays becoming increasingly popular in mice. However, carefully looking through the literature, marked differences in disease severity could be observed. In fact, while setting up the L-arginine (2×4 g/kg i.p.)-induced AP model in BALB/c mice, we found a relatively low rate (around 15%) of pancreatic necrosis, whereas others have detected much higher rates (up to 55%). We suspected that this may be due to differences between mouse strains. We administered various concentrations (5–30%, pH = 7.4) and doses (2×4, 3×3, or 4×2.5 g/kg) of L-arginine-HCl in BALB/c, FVB/n and C57BL/6 mice. The potential gender-specific effect of L-arginine was investigated in C57BL/6 mice. The fate of mice in response to the i.p. injections of L arginine followed one of three courses. Some mice (1) developed severe AP or (2) remained AP-free by 72 h, whereas others (3) had to be euthanized (to avoid their death, which was caused by the high dose of L-arginine and not AP) within 12 h. , In FVB/n and C57BL/6 mice, the pancreatic necrosis rate (about 50%) was significantly higher than that observed in BALB/c mice using 2×4 g/kg 10% L–arginine, but euthanasia was necessary in a large proportion of animals, The i.p. injection of lower L-arginine concentrations (e.g. 5–8%) in case of the 2×4 g/kg dose, or other L-arginine doses (3×3 or 4×2.5 g/kg, 10%) were better for inducing AP. We could not detect any significant differences between the AP severity of male and female mice. Taken together, when setting up the L-arginine-induced AP model, there are several important factors that are worth consideration such as the dose and concentration of the administered L arginine-HCl solution and also the strain of mice.
OntoHarvester : An Unsupervised Ontology Generator from Free Text

Ontologies are a vital component of most knowledge-based applications, such as semantic web search, intelligent information integration, and natural language processing. In the last two decades, many manual or highly supervised techniques were proposed to generate domain-specific ontologies. However, these approaches are usually very time-consuming and resource-demanding, and thus not scalable. To address this issue, numerous approaches have been recently proposed to automatically generate ontologies. These approaches mostly employ statistical or shallow NLP-based methods which usually limit the quality of their results. In this paper, we introduce OntoHarvester, a deep NLP-based system to automatically extract and populate domain-specific ontologies from morphological structures in the free text. Using our text mining framework, called SemScape, OntoHarvester converts text into graph structures called TextGraphs in which nodes represent candidate terms in the text and edges represent grammatical relations between the terms. Unlike most existing techniques that separate the concept extraction process from the semantic relation extraction, OntoHarvester integrates these two processes by starting with a small seed of domain’s concepts and iteratively performing the following two steps. i) Using graph-based patterns over the TextGraphs, it finds taxonomic relations between the concepts in the current ontology and other candidate terms. ii) From the candidate terms found in the previous step, OntoHarvester adds highly frequent and confident ones to the current ontology. OntoHarvester repeats the above two steps until the number of newly extracted concepts is smaller than a pre-defined threshold. This incremental process makes OntoHarvester more focused on the specified domain and more robust to noise. Our extended evaluation indicates that OntoHarvester improves the accuracy and coverage with respect to the existing methods, and starting from small initial seeds, it provides high-quality results for different domains.
Targeting transgene expression to antigen-presenting cells derived from lentivirus-transduced engrafting human hematopoietic stem/progenitor cells.

Hematopoietic stem cells (HSCs) represent an important target for the treatment of various blood disorders. As the source of critical cells within the immune system, genetic modification of HSCs can also be used to modulate immune responses. The effectiveness of HSC-mediated gene therapy largely depends on efficient gene delivery into long-term repopulating progenitors and targeted transgene expression in an appropriate progeny of the transduced pluripotent HSCs. Self-inactivating (SIN) lentiviral vectors have been demonstrated to be capable of transducing mitotically inactive cells, including HSCs, and accommodating a nonviral promoter to control the transgene expression in transduced cells. In this study, we constructed 2 SIN lentiviral vectors, EF.GFP and DR.GFP, to express the green fluorescent protein (GFP) gene controlled solely by the promoter of either a housekeeping gene EF-1alpha or the human HLA-DRalpha gene, which is selectively expressed in antigen-presenting cells (APCs). We demonstrated that both vectors efficiently transduced human pluripotent CD34+ cells capable of engrafting nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice. When the EF.GFP vector was used, constitutive high-level GFP expression was obtained in all the human HSC progeny detectable in NOD/SCID mice and in subsequent in vitro differentiation assays, indicating that engrafting human HSCs have been transduced. In contrast, the DR.GFP vector mediated transgene expression specifically in human HLA-DR+ cells and highly in differentiated dendritic cells (DCs), which are critical in regulating immunity. Furthermore, human DCs derived from transduced and engrafted human cells potently stimulated allogeneic T-cell proliferation. This study demonstrated successful targeting of transgene expression to APCs/DCs after stable gene transduction of pluripotent HSCs.
URBAN–RURAL CONTRASTS IN EXPLANATORY MODELS AND TREATMENT-SEEKING BEHAVIOURS FOR STROKE IN TANZANIA

Summary Stroke is an emerging problem in sub-Saharan Africa, about which little is known since most research to date has been based on retrospective, hospital-based studies. This anthropological work, designed to complement a large community-based project on stroke incidence, focuses on local understandings and treatment-seeking behaviours in urban (Dar-es-Salaam) and rural (Hai) areas of Tanzania. Semi-structured interviews (n=80) were conducted with 20 stroke patients, 20 relatives of stroke patients, ten traditional healers, and 30 other local residents. In contrast to common expectations, and literature that finds witchcraft beliefs to be most common in rural areas, stroke in urban Dar was widely believed to emanate from supernatural causes (demons and witchcraft), while in rural Hai, explanations drew mostly on ‘natural’ causes (hypertension, fatty foods, stress). These different beliefs and explanatory models fed into treatment-seeking behaviours. The first option in Hai was hospital treatment, while in Dar-es-Salaam, where belief in demons led to hospital avoidance, it was traditional healers. In both sites, multiple treatment options (serially or simultaneously) were the norm. Analysis of patient and carer narratives suggested that causation beliefs outweighed other factors, such as cost and distance, in shaping effective treatment. Three policy implications are drawn. First, as other studies have also shown, it is important to engage with, rather than dismiss, local explanations and interpretations of stroke. Stroke awareness messages need to take into account the geographical and belief systems differences. Developing an understanding of explanatory models that recognizes that local beliefs arise from dynamic processes of social interaction will be critical to designing effective interventions. Second, there is a clear role for multiple healing systems with possibility of cross-reference in the case of a chronic, disabling condition like stroke, since biomedical treatment cannot offer a ‘quick fix’ while traditional healers can help people come to terms with their condition. Third, issues of communication between health services and their patients are particularly critical.
The Utility of the Tip–Apex Distance in Predicting Axial Migration and Cutout With the Trochanteric Fixation Nail System Helical Blade

Objectives: To determine whether a tip–apex distance (TAD) <20 mm is associated with a higher rate of axial migration and perforation with the Trochanteric Fixation Nail (TFN) System helical blade implant. Design: Retrospective. Setting: Level I Trauma Center. Participants: Four hundred forty‐three patients surgically treated for proximal femur fractures were identified through a query of Current Procedural Terminology code 27245 from January 2009 to February 2013. A total of 258 patients treated with the TFN helical blade system were included in the study. Main Outcome Measured: The association of axial migration and perforation with the measured TAD. Results: The overall rate of mechanical complications was 10.1%. The average TAD was 20.4 mm. Axial perforation occurred in 8 patients (3.4%). Axial migration up to subchondral bone without perforation occurred in 3 patients (1.1%). Only 1 fracture failed in varus (0.38%). There was a significant difference in the rates of combined axial migration and perforation with a TAD <20 mm (P = 0.03). Logistic regression model demonstrated increased odds for combined axial cutout and migration with TAD less than 20 (odds ratio = 1.15, P = 0.01). Conclusions: A TAD <20 mm was associated with an increased frequency of axial migration and cutout with the TFN helical blade. Level of Evidence: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.
Transmural Dispersion of Repolarization in Failing and Nonfailing Human Ventricle

Rationale: Transmural dispersion of repolarization has been shown to play a role in the genesis of ventricular tachycardia and fibrillation in different animal models of heart failure (HF). Heterogeneous changes of repolarization within the midmyocardial population of ventricular cells have been considered an important contributor to the HF phenotype. However, there is limited electrophysiological data from the human heart. Objective: To study electrophysiological remodeling of transmural repolarization in the failing and nonfailing human hearts. Methods and Results: We optically mapped the action potential duration (APD) in the coronary-perfused scar-free posterior-lateral left ventricular free wall wedge preparations from failing (n=5) and nonfailing (n=5) human hearts. During slow pacing (S1S1=2000 ms), in the nonfailing hearts we observed significant transmural APD gradient: subepicardial, midmyocardial, and subendocardial APD80 were 383±21, 455±20, and 494±22 ms, respectively. In 60% of nonfailing hearts (3 of 5), we found midmyocardial islands of cells that presented a distinctly long APD (537±40 ms) and a steep local APD gradient (27±7 ms/mm) compared with the neighboring myocardium. HF resulted in prolongation of APD80: 477±22 ms, 495±29 ms, and 506±35 ms for the subepi-, mid-, and subendocardium, respectively, while reducing transmural APD80 difference from 111±13 to 29±6 ms (P<0.005) and presence of any prominent local APD gradient. In HF, immunostaining revealed a significant reduction of connexin43 expression on the subepicardium. Conclusions: We present for the first time direct experimental evidence of a transmural APD gradient in the human heart. HF results in the heterogeneous prolongation of APD, which significantly reduces the transmural and local APD gradients.
The Diagnostic Challenge Competition: Probabilistic Techniques for Fault Diagnosis in Electrical Power Systems

Reliable systems health management is an important research area of NASA. A health management system that can accurately and quickly diagnose faults in various on-board systems of a vehicle will play a key role in the success of current and future NASA missions. We introduce in this paper the ProDiagnose algorithm, a diagnostic algorithm that uses a probabilistic approach, accomplished with Bayesian Network models compiled to Arithmetic Circuits, to diagnose these systems. We describe the ProDiagnose algorithm, how it works, and the probabilistic models involved. We show by experimentation on two Electrical Power Systems based on the ADAPT testbed, used in the Diagnostic Challenge Competition (DX 09), that ProDiagnose can produce results with over 96% accuracy and less than 1 second mean diagnostic time.
Psychological Therapies for Auditory Hallucinations (Voices): Current Status and Key Directions for Future Research

This report from the International Consortium on Hallucinations Research considers the current status and future directions in research on psychological therapies targeting auditory hallucinations (hearing voices). Therapy approaches have evolved from behavioral and coping-focused interventions, through formulation-driven interventions using methods from cognitive therapy, to a number of contemporary developments. Recent developments include the application of acceptance- and mindfulness-based approaches, and consolidation of methods for working with connections between voices and views of self, others, relationships and personal history. In this article, we discuss the development of therapies for voices and review the empirical findings. This review shows that psychological therapies are broadly effective for people with positive symptoms, but that more research is required to understand the specific application of therapies to voices. Six key research directions are identified: (1) moving beyond the focus on overall efficacy to understand specific therapeutic processes targeting voices, (2) better targeting psychological processes associated with voices such as trauma, cognitive mechanisms, and personal recovery, (3) more focused measurement of the intended outcomes of therapy, (4) understanding individual differences among voice hearers, (5) extending beyond a focus on voices and schizophrenia into other populations and sensory modalities, and (6) shaping interventions for service implementation.
Diaspore bank analysis of Baltic coastal waters

Abstract The coastal waters are important transition zones for terrestrial nutrient and pollutant runoff and the open Sea. During the last decades, eutrophication has negatively influenced macrophyte communities of the coastal ecosystems, making restoration activities inevitable. This study analysed recent macrophyte vegetation and the reproductive potential through the sediment diaspore reservoir along the German Baltic Sea coastline. Salinity was identified to be the responsible factor for shifts in the macrophyte community with most commonly found species like Stuckenia pectinata or Myriophyllum spicatum. In contrast, the oospores of small charophytes (e.g. Tolypella nidifica) clearly dominated the sediment diaspore bank. The germination rates differed in the recent vegetation composition and the diaspore bank composition with Zannichellia palustris as the dominant species. However, several species not visually detected at the respective sites were represented in the diaspore bank and germinated at a low rate (e.g. Chara contraria and Lamprothamnium papulosum). The maximal germination frequency corresponded to the sediment layer in which diaspore density was the highest (5–15 cm). In conclusion, the germinable diaspores were observed at all sites. Considering the differences between the diaspore composition, recent vegetation and germination success, we have illustrated the potential of the diaspore banks for the restoration of the macrophyte communities after at least mid-term periods of disturbance.
Relative efficacy of human monocytes and dendritic cells as accessory cells for T cell replication

Monocyte-specific monoclonal antibodies (7) were used to compare the efficacy of monocytes and dendritic cells as accessory or stimulator cells for human T cell replication. Both unfractionated and plastic- adherent mononuclear cells were first treated with a cytolytic antimonocyte antibody that kills greater than 95% of monocytes but not dendritic cells. When tested as stimulators of the mixed leukocyte reaction (MLR) and of oxidative mitogenesis (the proliferation of T cells modified with sodium periodate), the monocyte-depleted cells had normal or enhanced stimulatory capacity. Monocyte-depleted mononuclear cells also proliferated normally to soluble antigens (Candida albicans, tetanus toxoid), even under limiting conditions of cell dose, antigen dose, and culture time. Adherent blood mononuclear cells were next separated into monocyte-enriched and -depleted components using fluoresceinated antimonocyte antibody and the cell sorter. The depleted fraction (less than 2% monocytes by esterase staining and by cytology) contained the dendritic cells and exhibited at least 75% of the accessory activity. The monocyte-rich fraction (approximately 97% esterase positive) stimulated the MLR and oxidative mitogenesis weakly, and was comparable in potency to nonadherent cells. Cell-specific antibodies and complement were also used to prepare dendritic cells that were thoroughly depleted of monocytes and lymphocytes. The dendritic cells (70-80% pure) were potent stimulators of the allogeneic MLR, syngeneic MLR, and tetanus toxoid response, being active at stimulator to responder ratios of 1:100 or less. Taken together with previous studies (1, 2), these experiments indicate that the dendritic cell is the major stimulator of T cell replication in man. The contribution of class II products of the major histocompatibility complex (7) was then evaluated with a new monoclonal, 9.3F10. Accessory function was dramatically inhibited if cells bearing class II antigens were killed with 9.3F10 and complement, or if class II molecules were blocked by the addition of 9.3F10 Fab to the culture medium. The expression of 9.3F10 class II products was therefore studied on purified monocytes and dendritic cells. Most if not all cells in both populations reacted with 9.3F10, and each population exhibited approximately 150,000 125I-Fab 9.3F10 binding sites per cell. Since Ia+ dendritic cells are active accessory cells, but Ia+ monocytes are not, class II products are necessary but not sufficient for the stimulation of T cell proliferation in man.
Oil and Water Can Mix: An Integration of Polyhedral and AST-Based Transformations

Optimizing compilers targeting modern multi-core machines require complex program restructuring to expose the best combinations of coarse- and fine-grain parallelism and data locality. The polyhedral compilation model has provided significant advancements in the seamless handling of compositions of loop transformations, thereby exposing multiple levels of parallelism and improving data reuse. However, it usually implements abstract optimization objectives, for example "maximize data reuse", which often does not deliver best performance, e.g., The complex loop structures generated can be detrimental to short-vector SIMD performance. In addition, several key transformations such as pipeline-parallelism and unroll-and-jam are difficult to express in the polyhedral framework. In this paper, we propose a novel optimization flow that combines polyhedral and syntactic/AST-based transformations. It generates high-performance code that contains regular loops which can be effectively vectorized, while still implementing sufficient parallelism and data reuse. It combines several transformation stages using both polyhedral and AST-based transformations, delivering performance improvements of up to 3× over the PoCC polyhedral compiler on Intel Nehalem and IBM Power7 multicore processors.
Structure and Protein–Protein Interactions of Methanol Dehydrogenase from Methylococcus capsulatus (Bath)

In the initial steps of their metabolic pathway, methanotrophic bacteria oxidize methane to methanol with methane monooxygenases (MMOs) and methanol to formaldehyde with methanol dehydrogenases (MDHs). Several lines of evidence suggest that the membrane-bound or particulate MMO (pMMO) and MDH interact to form a metabolic supercomplex. To further investigate the possible existence of such a supercomplex, native MDH from Methylococcus capsulatus (Bath) has been purified and characterized by size exclusion chromatography with multi-angle light scattering and X-ray crystallography. M. capsulatus (Bath) MDH is primarily a dimer in solution, although an oligomeric species with a molecular mass of ∼450–560 kDa forms at higher protein concentrations. The 2.57 Å resolution crystal structure reveals an overall fold and α2β2 dimeric architecture similar to those of other MDH structures. In addition, biolayer interferometry studies demonstrate specific protein–protein interactions between MDH and M. capsulatus (Bath) pMMO as well as between MDH and the truncated recombinant periplasmic domains of M. capsulatus (Bath) pMMO (spmoB). These interactions exhibit KD values of 833 ± 409 nM and 9.0 ± 7.7 μM, respectively. The biochemical data combined with analysis of the crystal lattice interactions observed in the MDH structure suggest a model in which MDH and pMMO associate not as a discrete, stoichiometric complex but as a larger assembly scaffolded by the intracytoplasmic membranes.