Miracle-dz/UniFAR-FTUs huggingface dataset:
ADX: a high field, high power density, advanced divertor and RF tokamak

The MIT Plasma Science and Fusion Center and collaborators are proposing a high-performance Advanced Divertor and RF tokamak eXperiment (ADX)—a tokamak specifically designed to address critical gaps in the world fusion research programme on the pathway to next-step devices: fusion nuclear science facility (FNSF), fusion pilot plant (FPP) and/or demonstration power plant (DEMO). This high-field (⩾6.5 T, 1.5 MA), high power density facility (P/S ∼ 1.5 MW m−2) will test innovative divertor ideas, including an ‘X-point target divertor’ concept, at the required performance parameters—reactor-level boundary plasma pressures, magnetic field strengths and parallel heat flux densities entering into the divertor region—while simultaneously producing high-performance core plasma conditions that are prototypical of a reactor: equilibrated and strongly coupled electrons and ions, regimes with low or no torque, and no fuelling from external heating and current drive systems. Equally important, the experimental platform will test innovative concepts for lower hybrid current drive and ion cyclotron range of frequency actuators with the unprecedented ability to deploy launch structures both on the low-magnetic-field side and the high-magnetic-field side—the latter being a location where energetic plasma–material interactions can be controlled and favourable RF wave physics leads to efficient current drive, current profile control, heating and flow drive. This triple combination—advanced divertors, advanced RF actuators, reactor-prototypical core plasma conditions—will enable ADX to explore enhanced core confinement physics, such as made possible by reversed central shear, using only the types of external drive systems that are considered viable for a fusion power plant. Such an integrated demonstration of high-performance core-divertor operation with steady-state sustainment would pave the way towards an attractive pilot plant, as envisioned in the ARC concept (affordable, robust, compact) (Sorbom et al 2015 Fusion Eng. Des. submitted (arXiv:1409.3540)) that makes use of high-temperature superconductor technology—a high-field (9.25 T) tokamak the size of the Joint European Torus that produces 270 MW of net electricity.
Heterogeneous cross domain ranking in latent space

Traditional ranking mainly focuses on one type of data source, and effective modeling still relies on a sufficiently large number of labeled or supervised examples. However, in many real-world applications, in particular with the rapid growth of the Web 2.0, ranking over multiple interrelated (heterogeneous) domains becomes a common situation, where in some domains we may have a large amount of training data while in some other domains we can only collect very little. One important question is: "if there is not sufficient supervision in the domain of interest, how could one borrow labeled information from a related but heterogenous domain to build an accurate model? ". This paper explores such an approach by bridging two heterogeneous domains via the latent space. We propose a regularized framework to simultaneously minimize two loss functions corresponding to two related but different information sources, by mapping each domain onto a "shared latent space", capturing similar and transferable oncepts. We solve this problem by optimizing the convex upper bound of the non-continuous loss function and derive its generalization bound. Experimental results on three different genres of data sets demonstrate the effectiveness of the proposed approach.
Testosterone-Dependent miR-26a-5p and let-7g-5p Act as Signaling Mediators to Regulate Sperm Apoptosis via Targeting PTEN and PMAIP1

Recent evidence suggests that testosterone deficiency can dramatically decrease the quality of sperm. MicroRNAs (miRNAs) are conserved mediators of post-transcriptional gene regulation in eukaryotes. However, the systemic regulation and function of miRNAs in sperm quality decline induced by testosterone deficiency has not been investigated. Here, we found that the sperm apoptosis was significantly enhanced and the sperm motility was dramatically decreased in hemicastrated pigs. We then used small RNA sequencing to detect miRNA profiles of sperm from pigs with prepubertal hemicastration (HC) and compared them with control libraries. We identified 16 differentially expressed (DE) miRNAs between the sperm of prepubertal HC and control (CT) pigs. Functional enrichment analysis indicated that the target genes of these DE miRNAs were mainly enriched in apoptosis-related pathways including the p53, mitogen-activated protein kinase (MAPK), and mammalian target of rapamycin (mTOR) pathways. Furthermore, gain- and loss-of-function analyses demonstrated potential anti-apoptotic effects of the DE miRNAs miR-26a-5p and let-7g-5p on sperm cells. The luciferase reporter assay confirmed that PTEN and PMAIP1 are targets of miR-26a-5p and let-7g-5p, respectively. Spearman’s correlation analysis revealed significantly positive correlations between the sperm and its corresponding seminal plasma exosomes regarding the miRNA expression levels. In conclusion, testosterone deficiency-induced changes in the miRNA components of seminal plasma exosomes secreted by the genital tract may partially elucidate sperm miRNAome alterations, which are further responsible for the decline of sperm motility.
Homeodomain Interacting Protein Kinase 2: A Target for Alzheimer's Beta Amyloid Leading to Misfolded p53 and Inappropriate Cell Survival

Background Homeodomain interacting protein kinase 2 (HIPK2) is an evolutionary conserved serine/threonine kinase whose activity is fundamental in maintaining wild-type p53 function, thereby controlling the destiny of cells when exposed to DNA damaging agents. We recently reported an altered conformational state of p53 in tissues from patients with Alzheimer's Disease (AD) that led to an impaired and dysfunctional response to stressors. Methodology/Principal Findings Here we examined the molecular mechanisms underlying the impairment of p53 activity in two cellular models, HEK-293 cells overexpressing the amyloid precursor protein and fibroblasts from AD patients, starting from recent findings showing that p53 conformation may be regulated by HIPK2. We demonstrated that beta-amyloid 1–40 induces HIPK2 degradation and alters HIPK2 binding activity to DNA, in turn regulating the p53 conformational state and vulnerability to a noxious stimulus. Expression of HIPK2 was analysed by western blot experiments, whereas HIPK2 DNA binding was examined by chromatin immunoprecipitation analysis. In particular, we evaluated the recruitment of HIPK2 onto some target promoters, including hypoxia inducible factor-1α and metallothionein 2A. Conclusions/Significance These results support the existence of a novel amyloid-based pathogenetic mechanism in AD potentially leading to the survival of injured dysfunctional cells.
Determination of the critical plane and durability estimation for a multiaxial cyclic loading

An analytical procedure is proposed to determine the critical plane orientation according to the Findley criterion for the multiaxial cyclic loading. The cases of in-phase and anti-phase cyclic loading are considered. Calculations of the stress state are carried out for the system of the gas turbine engine compressor disk and blades for flight loading cycles. The formulas obtained are used for estimations of the fatigue durability of this essential element of structure.
Phosphorylation of Threonine 175 Tau in the Induction of Tau Pathology in Amyotrophic Lateral Sclerosis—Frontotemporal Spectrum Disorder (ALS-FTSD). A Review

Approximately 50–60% of all patients with amyotrophic lateral sclerosis (ALS) will develop a deficit of frontotemporal function, ranging from frontotemporal dementia (FTD) to one or more deficits of neuropsychological, speech or language function which are collectively known as the frontotemporal spectrum disorders of ALS (ALS-FTSD). While the neuropathology underlying these disorders is most consistent with a widespread alteration in the metabolism of transactive response DNA-binding protein 43 (TDP-43), in both ALS with cognitive impairment (ALSci) and ALS with FTD (ALS-FTD; also known as MND-FTD) there is evidence for alterations in the metabolism of the microtubule associated protein tau. This alteration in tau metabolism is characterized by pathological phosphorylation at residue Thr175 (pThr175 tau) which in vitro is associated with activation of GSK3β (pTyr216GSK3β), phosphorylation of Thr231tau, and the formation of cytoplasmic inclusions with increased rates of cell death. This putative pathway of pThr175 induction of pThr231 and the formation of pathogenic tau inclusions has been recently shown to span a broad range of tauopathies, including chronic traumatic encephalopathy (CTE) and CTE in association with ALS (CTE-ALS). This pathway can be experimentally triggered through a moderate traumatic brain injury, suggesting that it is a primary neuropathological event and not secondary to a more widespread neuronal dysfunction. In this review, we discuss the neuropathological underpinnings of the postulate that ALS is associated with a tauopathy which manifests as a FTSD, and examine possible mechanisms by which phosphorylation at Thr175tau is induced. We hypothesize that this might lead to an unfolding of the hairpin structure of tau, activation of GSK3β and pathological tau fibril formation through the induction of cis-Thr231 tau conformers. A potential role of TDP-43 acting synergistically with pathological tau metabolism is proposed.
Expressions of matrix metalloproteinase 9 and tissue inhibitor of metalloproteinases 1 in lung tissues of neonatal rats with intrauterine infection

Objective: To investigate the changes and mechanisms of matrix metallopeptidase 9 (MMP-9) and tissue inhibitor of metalloproteinases 1 (TIMP-1) in the lung tissues of neonatal rats with intrauterine infection (II). Methods: The pregnant rats were divided into the intrauterine infection group (group LPS) and the control group (group NS). The rats in group LPS were intraperitoneally injected lipopolysaccharide (LPS) to establish the II animal model; the neonatal rats of the two groups were selected on D1, D3, D7, and D14 after birth for the HE staining and radiation alveolar count (RAC); meanwhile, the protein expression and mRNA quantification of MMP-9 and TIMP-1 in the lung tissues were detected. Results: Group LPS showed significantly increased infiltration of alveolar inflammatory cells and decreased RAC than group NS. The protein and mRNA expressions of MMP-9 in group LPS were significantly higher than group NS on D3, D7, and D14, and those expressions in group LPS showed no significant difference. The protein and mRNA expressions of TIMP-1 in group LPS were gradually increased after birth, and showed significant difference with group NS on D3, D7, and D14. Conclusions: The post-II expressions of MMP-9 and TIMP-1 in the lung tissues of the neonatal rats were significantly increased, and its imbalance might play an important role in repairing lung injuries and abnormalities.
Comparison of the RGD Motif–Containing αvβ6 Integrin–Binding Peptides SFLAP3 and SFITGv6 for Diagnostic Application in HNSCC

αvβ6 integrin is overexpressed by several carcinomas and thus considered a target for diagnostic imaging and anticancer therapies. Recently, we presented the αvβ6 integrin-binding peptide SFITGv6 as a novel potential tracer for imaging and targeted therapy of αvβ6 integrin–positive carcinomas. Here, we analyzed the affinity and specificity of 5 native αvβ6 integrin–specific binders in comparison to SFITGv6. Methods: Sunflower trypsin inhibitor 1 (SFTI1)–based peptides containing arginine-glycine-aspartic acid (RGD) motif-spanning octamers of fibronectin (SFFN1), tenascin C (SFTNC), vitronectin (SFVTN), and latency-associated peptides (LAP) 1 (SFLAP1) and 3 (SFLAP3) were synthesized, and their binding potential to αvβ6 integrin–expressing head and neck squamous cell carcinoma (HNSCC) cell lines was evaluated. Subsequently, stability, affinity, and specificity were assessed in vitro using radio–high-pressure liquid chromatography, surface plasmon resonance assay, and binding experiments including competition, kinetics, internalization, and efflux. αvβ6 integrin binding specificity was further evaluated by peptide histochemistry. Finally, in vivo binding properties were assessed using small-animal PET imaging and biodistribution experiments in HNSCC-bearing mice, and 68Ga-DOTA-SFLAP3 was applied for diagnostic PET/CT of an HNSCC patient. Results: When the newly designed peptides were compared, significant binding (>20%) to several HNSCC cell lines (HNO97, HNO399, and HNO223) and a fast internalization of up to 60% and 70% were observed for SFLAP3 (GRGDLGRL) and SFITGv6 (FRGDLMQL). In contrast, the other peptides displayed binding that was moderate (SFLAP1, 4.1%–12.1%) to marginal (SFFN1, SFTNC, and SFVTN, <1%) and were therefore excluded from further analysis. Notably, SFLAP3 exhibited improved affinity for αvβ6 integrin (mean half-maximal inhibitory concentration, 3.5 nM; dissociation constant, 7.4). Moreover, small-animal PET imaging and biodistribution studies of HNSCC xenograft mice revealed an increased tumor-specific accumulation 30–60 min after injection of 68Ga-labeled or 177Lu-labeled DOTA-SFLAP3. Peptide staining further demonstrated binding specificity for SFLAP3 to HNSCC tumor cells. Finally, PET/CT scanning of an HNSCC patient showed specific SFLAP3 accumulation in the primary tumor lesion (SUVmax, 5.1) and in corresponding lymph node metastases (SUVmax, 4.1). Conclusion: SFLAP3 represents a promising tracer for prognostic assessment, diagnostic imaging, and possibly targeted therapy of αvβ6 integrin–expressing tumors.
Rapid Adaptation to Climate Facilitates Range Expansion of an Invasive Plant

Invade and Adapt The mechanisms by which plant and animal species spread into new habitats have become an increasing focus of ecological research, particularly in the context of climate change and species invasions. Colautti and Barrett (p. 364) examined the ecological consequence of local adaptation evolving rapidly along a 1000-kilometer climatic gradient in purple loosestrife (Lythrum salicaria), one of the most notorious invasive plant species in North America. These invasive populations have evolved to become locally adapted within 50 to 100 years with important ecological consequences—increasing reproductive output by more than an order of magnitude. Invasive populations of purple loosestrife in eastern North America have evolved increased fitness at the invasion front. Adaptation to climate, evolving over contemporary time scales, could facilitate rapid range expansion across environmental gradients. Here, we examine local adaptation along a climatic gradient in the North American invasive plant Lythrum salicaria. We show that the evolution of earlier flowering is adaptive at the northern invasion front where it increases fitness as much as, or more than, the effects of enemy release and the evolution of increased competitive ability. However, early flowering decreases investment in vegetative growth, which reduces fitness by a factor of 3 in southern environments where the North American invasion commenced. Our results demonstrate that local adaptation can evolve quickly during range expansion, overcoming environmental constraints on propagule production.
Time and Money: Substitutes in Real Terms and Complements in Satisfactions

Time and money are basic commodities in the utility function and are substitutes in real terms. To a certain extent, having time and money is a matter of either/or, depending on individual preferences and budget constraints. However, satisfaction with time and satisfaction with money are typically complements, i.e., individuals tend to be equally satisfied with both domains. In this paper, we provide an explanation for this apparent paradox through the analysis of the simultaneous determination of economic satisfaction and leisure satisfaction. We test some hypotheses, including the hypothesis that leisure satisfaction depends on both the quantity and quality of leisure-where quality is proxied by good intensiveness and social intensiveness. Our results show that both the quantity and the quality of leisure are important determinants of leisure satisfaction, and, since having money contributes to the quality of leisure, this explains the empirical findings of the satisfactions being complementary at the same time as the domains are substitutes. Interestingly, gender matters. Intra-household effects and especially individual characteristics are more pronounced for women than for men for both domain satisfactions. Additionally, good intensiveness is more important for men (e.g., housing conditions), whereas social intensiveness is more important for women (e.g., the presence of children and participation in leisure-time activities).
Variation of Self‐Incompatibility within Invasive Populations of Purple Loosestrife (Lythrum salicaria L.) from Eastern North America

Colonization may favor self‐compatibility (SC) in invasive plants, a process consistent with Baker’s law. We investigated this hypothesis in invasive eastern North American populations of tristylous Lythrum salicaria L. (purple loosestrife) by controlled self‐ and cross‐pollinations of 124 plants sampled from 12 populations grown under uniform glasshouse conditions. We evaluated whether populations at the northern front of the invasion exhibited higher levels of SC than southern populations, which are closer to source populations for the North American invasion. We also sought evidence for morph‐specific differences in the strength of trimorphic incompatibility. We used the ASTER statistical program to jointly model three measures of SC: (1) the probability of producing at least one seed following self‐pollination, (2) the number of fruits produced by self‐pollination, and (3) the average number of seeds per fruit resulting from self‐pollination. Just over one‐quarter of plants set at least one fruit after self‐pollination, and there was a significant effect of style morph on variation in SC, with the mid‐styled morph most compatible. Although variation for SC was detected in 11 of the 12 populations, there was no evidence that SC increased toward the northern range limit as a result of the invasion process.
Lidocaine Does Not Depress Reflex Di lat ion of the Pupil Merlin

Background and Objectives. Pupillary dilation in response to dermatomal electrical stimulation is one method of determining sensory block level during combined epidural and general anesthesia. Use of this technique may, however, be confounded by systemic absorption of epidurally administered local anesthetics. Accordingly, the effects of intravenous lidocaine on the magnitude and duration of reflex pupillary dilation were evaluated. Methods. Six volunteers were each anesthetized twice with desflurane 3.5-6.0%. During one anesthetic, intravenous lidocaine was administered to a plasma concentration of 5.3 + 1.5 ~g/mL. When the plasma concentrations were stable, a 5-second tetanic electrical stimulus was applied. Pupil size was then recorded for 8 minutes. Results. Lidocaine, at plasma concentrations near 5 ~g/mL, did not significantly alter the pupillary response to electrical stimulation. In contrast, stimulus-induced increase in heart rate was obliterated. Painful stimulation did not increase systolic blood pressure in either case. Conclusions. Typical plasma lidocaine concentrations observed during epidural anesthesia are unlikely to prevent the use of pupillary responses to evaluate sensory block level. Reg. Anesth 1997: 22: 461--465.
Multipotent hair follicle stem cells promote repair of spinal cord injury and recovery of walking function

The mouse hair follicle is an easily accessible source of actively growing, pluripotent adult stem cells. C57BL transgenic mice, labeled with the fluorescent protein GFP, afforded follicle stem cells whose fate could be followed when transferred to recipient animals. These cells appear to be relatively undifferentiated since they are positive for the stem cell markers nestin and CD34 but negative for the keratinocyte marker keratin 15. These hair follicle stem cells can differentiate into neurons, glia, keratinocytes, smooth muscle cells, and melanocytes in vitro. Implanting hair follicle stem cells into the gap region of severed sciatic or tibial nerves greatly enhanced the rate of nerve regeneration and restoration of nerve function. The transplanted follicle cells transdifferentiated mostly into Schwann cells, which are known to support neuron regrowth. The treated mice regained the ability to walk essentially normally. In the present study, we severed the thoracic spinal chord of C57BL/6 immunocompetent mice and transplanted GFP-expressing hair follicle stem cells to the injury site. Most of the transplanted cells also differentiated into Schwann cells that apparently facilitated repair of the severed spinal cord. The rejoined spinal cord reestablished extensive hind-limb locomotor performance. These results suggest that hair follicle stem cells can promote the recovery of spinal cord injury. Thus, hair follicle stem cells provide an effective accessible, autologous source of stem cells for the promising treatment of peripheral nerve and spinal cord injury.
The phenazine pyocyanin is a terminal signalling factor in the quorum sensing network of Pseudomonas aeruginosa

Certain members of the fluorescent pseudomonads produce and secrete phenazines. These heterocyclic, redox‐active compounds are toxic to competing organisms, and the cause of these antibiotic effects has been the focus of intense research efforts. It is largely unknown, however, how pseudomonads themselves respond to – and survive in the presence of – these compounds. Using Pseudomonas aeruginosa DNA microarrays and quantitative RT‐PCR, we demonstrate that the phenazine pyocyanin elicits the upregulation of genes/operons that function in transport [such as the resistance‐nodulation‐cell division (RND) efflux pump MexGHI‐OpmD] and possibly in redox control (such as PA2274, a putative flavin‐dependant monooxygenase), and downregulates genes involved in ferric iron acquisition. Strikingly, mexGHI‐opmD and PA2274 were previously shown to be regulated by the PA14 quorum sensing network that controls the production of virulence factors (including phenazines). Through mutational analysis, we show that pyocyanin is the physiological signal for the upregulation of these quorum sensing‐controlled genes during stationary phase and that the response is mediated by the transcription factor SoxR. Our results implicate phenazines as signalling molecules in both P. aeruginosa PA14 and PAO1.