Miracle-dz/UniFAR-FTUs huggingface dataset:
Simultaneous inhibition of mTORC1 and mTORC2 by mTOR kinase inhibitor AZD8055 induces autophagy and cell death in cancer cells

mTOR is a major biological switch, coordinating an adequate response to changes in energy uptake (amino acids, glucose), growth signals (hormones, growth factors) and environmental stress. mTOR kinase is highly conserved through evolution from yeast to man and in both cases, controls autophagy and cellular translation in response to nutrient stress. mTOR kinase is the catalytic component of two distinct multiprotein complexes called mTORC1 and mTORC2. In addition to mTOR, mTORC1 contains Raptor, mLST8 and PRAS40. mTORC2 contains mTOR, Rictor, mSIN1 and Protor-1. mTORC1 activates p70S6K, which in turn phosphorylates the ribosomal protein S6 and 4E-BP1, both involved in protein translation. mTORC2 activates AKT directly by phosphorylating Serine 473. pAKT(S473) phosphorylates TSC2 (tuberin) and inactivates it, preventing its association with TSC1 (hamartin) and the inhibition of Rheb, an activator of mTOR. pAKT also phosphorylates PRAS40, releasing it from the mTORC1 complex, increasing its kinase activity. Finally, AKT regulates FOXO3 phosphorylation, sequestering it in the cytosol in an inactive state.
Recovering galaxy star formation and metallicity histories from spectra using VESPA

We introduce versatile spectral analysis (VESPA): a new method which aims to recover robust star formation and metallicity histories from galactic spectra. VESPA uses the full spectral range to construct a galaxy history from synthetic models. We investigate the use of an adaptative parametrization grid to recover reliable star formation histories on a galaxy-by-galaxy basis. Our goal is robustness as opposed to high-resolution histories, and the method is designed to return high time resolution only where the data demand it. In this paper we detail the method and we present our findings when we apply VESPA to synthetic and real Sloan Digital Sky Survey (SDSS) spectroscopic data. We show that the number of parameters that can be recovered from a spectrum depends strongly on the signal-to-noise ratio, wavelength coverage and presence or absence of a young population. For a typical SDSS sample of galaxies, we can normally recover between two and five stellar populations. We find very good agreement between VESPA and our previous analysis of the SDSS sample with MOPED.
Experimental aspects of colour reconnection

This report summarises experimental aspects of the phenomena of colour reconnection in W + W production, concentrating on charged multiplicity and event shapes, which were carried out as part of the \Phenomenology Workshop on LEP2 Physics, Oxford, Physics Department and Keble College", 14{18 April, 1997. The work includes new estimates of the systematic uncertainty which may be attributed to colour reconnection eects in experimental measurements of MW.
Antioxidant N-acetylcysteine restores systemic nitric oxide availability and corrects depressions in arterial blood pressure and heart rate in diabetic rats

Increased oxidative stress and reduced nitric oxide (NO) bioactivity are key features of diabetes mellitus that eventually result in cardiovascular abnormalities. We assessed whether N-acetylcysteine (NAC), an antioxidant and glutathione precursor, could prevent the hyperglycaemia induced increase in oxidative stress, restore NO availability and prevent depression of arterial blood pressure and heart rate in vivo in experimental diabetes. Control (C) and streptozotocin-induced diabetic (D) rats were treated or not treated with NAC in drinking water for 8 weeks, initiated 1 week after induction of diabetes. At termination, plasma levels of free 15-F2t-isoprostane, a specific marker of oxygen free radical induced lipid peroxidation, was increased while the plasma total antioxidant concentration was decreased in untreated diabetic rats as compared to control rats (P < 0.05). This was accompanied by a significant reduction of plasma levels of nitrate and nitrite, stable metabolites of NO, (P < 0.05, D vs. C) and a reduced endothelial NO synthase protein expression in the heart and in aortic and mesenteric artery tissues. Systolic, diastolic and mean arterial blood pressures (SBP, DBP and MAP) and heart rate (HR) were reduced in diabetic rats (P < 0.05 vs. C) and NAC normalised the changes that occurred in the diabetic rats. The protective effects may be attributable to restoration of NO bioavailability in the circulation.
High-sensitivity simultaneous pressure and temperature sensor using a superstructure fiber grating

In this paper, we show that both pressure and temperature can be measured simultaneously by using a high-sensitivity fiber sensor. This sensor has a superstructure fiber grating (SFG) encapsulated in a polymer-half-filled metal cylinder, which has two openings on opposite sides of the wall of the polymer, to sense the pressure. The sensed pressure is transferred into axial extended-strain. The variation of pressures and temperatures will cause the variation of the center-wavelength and reflection of the SFG simultaneously due to the optical response of the SFG composed by the fiber Bragg grating (FBG) as well as long-period grating (LPG). Thus, the sensor can be used for measuring pressure and temperature simultaneously. It has a pressure sensitivity of 3 times 10-2 MPa-1, better than that using only a bare FBG. Temperature sensitivities in both 0.02 nm per degC and 0.16 dBm per degC have experimentally been obtained. This fiber sensor can be applied for boiler as well as for the underwater depth measurement
Detection of Viral DNA and Immune Responses to the Human Herpesvirus 6 101-Kilodalton Virion Protein in Patients with Multiple Sclerosis and in Controls

ABSTRACT Human herpesvirus 6 (HHV-6), a latent lymphotropic and neurotropic virus, has been suspected as an etiologic agent in multiple sclerosis (MS). The study was undertaken to correlate virologic evidence for HHV-6 activity with the state of host immunity to HHV-6 in MS patients and control subjects. The study revealed that cell-free DNA of HHV-6 was detected more frequently in both serum and cerebrospinal fluid of MS patients than in those of control subjects. T cells recognizing the recombinant 101-kDa protein (101K) corresponding to the major immunoreactive region unique to HHV-6 occurred at significantly lower precursor frequency in MS patients than in control subjects. The resulting HHV-6-specific T-cell lines obtained from MS patients exhibited skewed cytokine profiles characterized by the inability to produce interleukin-4 (IL-4) and IL-10. The decreased T-cell responses to HHV-6 and the altered cytokine profile were consistent with significantly declined serum immunoglobulin G (IgG) titers for HHV-6 of MS patients compared to those of control subjects. In contrast, elevated serum IgM titers for HHV-6 were detected in the majority of MS patients, which may reflect frequent exposure of B cells to HHV-6. The findings suggest that the decreased immune responses to HHV-6 may be responsible for ineffective clearance of HHV-6 in MS patients.
Advance directives and nominated representatives: A critique

With the ratification of the landmark United Nations Convention on Rights of Persons with Disabilities by India, it was imperative to revamp the mental health-care legislation, among other changes. Most notably, a presumption of mental capacity has been introduced, which means a paradigm shift in the client and provider relationship. The Mental Healthcare Act, 2017 empowers all persons to make advance directives (AD) and nominate representatives for shared decision-making. Psychiatric ADs (PADs) also seem to improve the information exchange between the care provider and the service user. PADs may also be used as a vehicle of consent to future treatments. While drafting the PAD, the drafter must also plan how such directed care would be financed. Insurance companies have not been mandated to comply with ADs. In the eventuality that the drafter's family refuse support for treatment specified in the PAD, the drafter would be left holding an unimplementable PAD. The AD saw its origins in the care of the terminally ill and decades later came to be utilized in mental health care. After nearly three decades of use in developed countries, evidence at best remains mixed or inconclusive. This review focuses on the AD from the Indian perspective.
Modulation of the Contrast Response Function by Electrical Microstimulation of the Macaque Frontal Eye Field

Spatial attention influences representations in visual cortical areas as well as perception. Some models predict a contrast gain, whereas others a response or activity gain when attention is directed to a contrast-varying stimulus. Recent evidence has indicated that microstimulating the frontal eye field (FEF) can produce modulations of cortical area V4 neuronal firing rates that resemble spatial attention-like effects, and we have shown similar modulations of functional magnetic resonance imaging (fMRI) activity throughout the visual system. Here, we used fMRI in awake, fixating monkeys to first measure the response in 12 visual cortical areas to stimuli of varying luminance contrast. Next, we simultaneously microstimulated subregions of the FEF with movement fields that overlapped the stimulus locations and measured how microstimulation modulated these contrast response functions (CRFs) throughout visual cortex. In general, we found evidence for a nonproportional scaling of the CRF under these conditions, resembling a contrast gain effect. Representations of low-contrast stimuli were enhanced by stimulation of the FEF below the threshold needed to evoke saccades, whereas high-contrast stimuli were unaffected or in some areas even suppressed. Furthermore, we measured a characteristic spatial pattern of enhancement and suppression across the cortical surface, from which we propose a simple schematic of this contrast-dependent fMRI response.
Phylogenomic Synteny Network Analysis of MADS-Box Transcription Factor Genes Reveals Lineage-Specific Transpositions, Ancient Tandem Duplications, and Deep Positional Conservation[OPEN]

Synteny-based network analyses provide new insight into the evolution of the MADS-box gene family. Conserved genomic context provides critical information for comparative evolutionary analysis. With the increase in numbers of sequenced plant genomes, synteny analysis can provide new insights into gene family evolution. Here, we exploit a network analysis approach to organize and interpret massive pairwise syntenic relationships. Specifically, we analyzed synteny networks of the MADS-box transcription factor gene family using 51 completed plant genomes. In combination with phylogenetic profiling, several novel evolutionary patterns were inferred and visualized from synteny network clusters. We found lineage-specific clusters that derive from transposition events for the regulators of floral development (APETALA3 and PI) and flowering time (FLC) in the Brassicales and for the regulators of root development (AGL17) in Poales. We also identified two large gene clusters that jointly encompass many key phenotypic regulatory Type II MADS-box gene clades (SEP1, SQUA, TM8, SEP3, FLC, AGL6, and TM3). Gene clustering and gene trees support the idea that these genes are derived from an ancient tandem gene duplication that likely predates the radiation of the seed plants and then expanded by subsequent polyploidy events. We also identified angiosperm-wide conservation of synteny of several other less studied clades. Combined, these findings provide new hypotheses for the genomic origins, biological conservation, and divergence of MADS-box gene family members.
Vision Screening for Children 36 to <72 Months: Recommended Practices

Purpose This article provides recommendations for screening children aged 36 to younger than 72 months for eye and visual system disorders. The recommendations were developed by the National Expert Panel to the National Center for Children’s Vision and Eye Health, sponsored by Prevent Blindness, and funded by the Maternal and Child Health Bureau of the Health Resources and Services Administration, United States Department of Health and Human Services. The recommendations describe both best and acceptable practice standards. Targeted vision disorders for screening are primarily amblyopia, strabismus, significant refractive error, and associated risk factors. The recommended screening tests are intended for use by lay screeners, nurses, and other personnel who screen children in educational, community, public health, or primary health care settings. Characteristics of children who should be examined by an optometrist or ophthalmologist rather than undergo vision screening are also described. Results There are two current best practice vision screening methods for children aged 36 to younger than 72 months: (1) monocular visual acuity testing using single HOTV letters or LEA Symbols surrounded by crowding bars at a 5-ft (1.5 m) test distance, with the child responding by either matching or naming, or (2) instrument-based testing using the Retinomax autorefractor or the SureSight Vision Screener with the Vision in Preschoolers Study data software installed (version 2.24 or 2.25 set to minus cylinder form). Using the Plusoptix Photoscreener is acceptable practice, as is adding stereoacuity testing using the PASS (Preschool Assessment of Stereopsis with a Smile) stereotest as a supplemental procedure to visual acuity testing or autorefraction. Conclusions The National Expert Panel recommends that children aged 36 to younger than 72 months be screened annually (best practice) or at least once (accepted minimum standard) using one of the best practice approaches. Technological updates will be maintained at http://nationalcenter.preventblindness. org.
Functional Redundancy and Complementarities of Seed Dispersal by the Last Neotropical Megafrugivores

Background Functional redundancy has been debated largely in ecology and conservation, yet we lack detailed empirical studies on the roles of functionally similar species in ecosystem function. Large bodied frugivores may disperse similar plant species and have strong impact on plant recruitment in tropical forests. The two largest frugivores in the neotropics, tapirs (Tapirus terrestris) and muriquis (Brachyteles arachnoides) are potential candidates for functional redundancy on seed dispersal effectiveness. Here we provide a comparison of the quantitative, qualitative and spatial effects on seed dispersal by these megafrugivores in a continuous Brazilian Atlantic forest. Methodology/Principal Findings We found a low overlap of plant species dispersed by both muriquis and tapirs. A group of 35 muriquis occupied an area of 850 ha and dispersed 5 times more plant species, and 13 times more seeds than 22 tapirs living in the same area. Muriquis dispersed 2.4 times more seeds in any random position than tapirs. This can be explained mainly because seed deposition by muriquis leaves less empty space than tapirs. However, tapirs are able to disperse larger seeds than muriquis and move them into sites not reached by primates, such as large forest gaps, open areas and fragments nearby. Based on published information we found 302 plant species that are dispersed by at least one of these megafrugivores in the Brazilian Atlantic forest. Conclusions/Significance Our study showed that both megafrugivores play complementary rather than redundant roles as seed dispersers. Although tapirs disperse fewer seeds and species than muriquis, they disperse larger-seeded species and in places not used by primates. The selective extinction of these megafrugivores will change the spatial seed rain they generate and may have negative effects on the recruitment of several plant species, particularly those with large seeds that have muriquis and tapirs as the last living seed dispersers.
Effects of temperature on transcriptome and cuticular hydrocarbon expression in ecologically differentiated populations of desert Drosophila

Abstract We assessed the effects of temperature differences on gene expression using whole‐transcriptome microarrays and cuticular hydrocarbon variation in populations of cactophilic Drosophila mojavensis. Four populations from Baja California and mainland Mexico and Arizona were each reared on two different host cacti, reared to sexual maturity on laboratory media, and adults were exposed for 12 hr to 15, 25, or 35°C. Temperature differences influenced the expression of 3,294 genes, while population differences and host plants affected >2,400 each in adult flies. Enriched, functionally related groups of genes whose expression changed at high temperatures included heat response genes, as well as genes affecting chromatin structure. Gene expression differences between mainland and peninsular populations included genes involved in metabolism of secondary compounds, mitochondrial activity, and tRNA synthases. Flies reared on the ancestral host plant, pitaya agria cactus, showed upregulation of genes involved in metabolism, while flies reared on organ pipe cactus had higher expression of DNA repair and chromatin remodeling genes. Population × environment (G × E) interactions had widespread effects on the transcriptome where population × temperature interactions affected the expression of >5,000 orthologs, and there were >4,000 orthologs that showed temperature × host plant interactions. Adults exposed to 35°C had lower amounts of most cuticular hydrocarbons than those exposed to 15 or 25°C, including abundant unsaturated alkadienes. For insects adapted to different host plants and climatic regimes, our results suggest that temperature shifts associated with climate change have large and significant effects on transcriptomes of genetically differentiated natural populations.
Representation of period doubling by digraphs and characteristic polynomials

A general procedure which defines a partial ordering of cyclic permutations induced by continuous maps is known for constructing immediate successors to a cycle. We expound on this procedure in terms of labelled digraphs and characteristic polynomials then apply this study to period doubling, the most common route to chaos for a nonlinear dynamical system.
Origins of heterogeneity in tissue perfusion and metabolism.

AIMS In the heart and other tissues, perfusion and metabolic activity are heterogeneous and spatially correlated. The goal of this work is to investigate the causes of this behaviour. Theoretical simulations are used to examine the effects on flow distribution and oxygen levels in terminal vascular beds of inherent irregularity in network structure, considering structural adaptation of vessel diameters to haemodynamic and metabolic stimuli, and adaptation of oxygen demand to local oxygen availability. METHODS AND RESULTS A mathematical model based on experimentally observed microvascular network structures (rat mesentery and m. sartorius) is used to simulate blood flow, oxygen transport, and adaptation of vessel diameters and tissue oxygen demand. Inherent geometric heterogeneities of vascular networks cause heterogeneity of blood flow and oxygen levels that cannot be eliminated by increasing metabolic sensitivity of diameter adaptation. Adaptation of oxygen demand to differences in oxygen availability causes increased oxygen extraction, implying improved functional capacity, and establishes a correlation between local oxygen demand and flow rate, as observed experimentally. Such a correlation is not predicted if the heterogeneity of oxygen demand is assumed to be an intrinsic tissue property. CONCLUSION A central mechanism generating heterogeneous perfusion is the inevitable structural heterogeneity of terminal vascular beds, which cannot be fully compensated by structural adaptation of vessel diameters. Heterogeneity of metabolism may result from adaptation of tissue function to the heterogeneous oxygen availability. These findings are of interest for the understanding of tissue function, including the heart, and of results obtained by corresponding imaging approaches.
Syndication to Overcome Transaction Costs of Cross-Border Investments? Evidence from a Worldwide Private Equity Deals` Dataset

Using a new dataset on worldwide private equity transactions we show that distance matters for this type of deals. The geographical investment patterns of private equity investors are considerably affected by transaction costs arising from long distances between these investors and their (potential) investments. However, the negative impact of long distances on private equity investors` funding decisions may be mitigated when far away investors syndicate with local partners. Also, inexperienced distant private equity financiers might profit from the know-how and local presence of veteran investors when they do joint deals. Syndication between foreign and local investors seems to be particularly strong in countries with developed private equity industries. Moreover, we demonstrate that transaction costs are more relevant for small than for large deals, pointing to their fixed-cost character.
Current-sourcing push-pull parallel-resonance inverter (CS-PPRI): theory and application as a discharge lamp driver

A novel topology, current-sourcing push-pull parallel-resonance inverter (CS-PPRI) was investigated theoretically and experimentally. The proposed power stage is built around a current fed push-pull inverter. The main features of the proposed inverter are: a load independent output current and zero voltage switching (ZVS). It is suggested that the proposed CS-PPRI is a viable alternative for realizing electronic ballasts for low and high-intensity discharge lamps. >
Genomic mosaicism with increased amyloid precursor protein (APP) gene copy number in single neurons from sporadic Alzheimer's disease brains

Previous reports have shown that individual neurons of the brain can display somatic genomic mosaicism of unknown function. In this study, we report altered genomic mosaicism in single, sporadic Alzheimer's disease (AD) neurons characterized by increases in DNA content and amyloid precursor protein (APP) gene copy number. AD cortical nuclei displayed large variability with average DNA content increases of ∼8% over non-diseased controls that were unrelated to trisomy 21. Two independent single-cell copy number analyses identified amplifications at the APP locus. The use of single-cell qPCR identified up to 12 copies of APP in sampled neurons. Peptide nucleic acid (PNA) probes targeting APP, combined with super-resolution microscopy detected primarily single fluorescent signals of variable intensity that paralleled single-cell qPCR analyses. These data identify somatic genomic changes in single neurons, affecting known and unknown loci, which are increased in sporadic AD, and further indicate functionality for genomic mosaicism in the CNS. DOI: http://dx.doi. org/10.7554/eLife.05116. 001
How Anesthetic, Analgesic and Other Non-Surgical Techniques During Cancer Surgery Might Affect Postoperative Oncologic Outcomes: A Summary of Current State of Evidence

The question of whether anesthetic, analgesic or other perioperative intervention during cancer resection surgery might influence long-term oncologic outcomes has generated much attention over the past 13 years. A wealth of experimental and observational clinical data have been published, but the results of prospective, randomized clinical trials are awaited. The European Union supports a pan-European network of researchers, clinicians and industry partners engaged in this question (COST Action 15204: Euro-Periscope). In this narrative review, members of the Euro-Periscope network briefly summarize the current state of evidence pertaining to the potential effects of the most commonly deployed anesthetic and analgesic techniques and other non-surgical interventions during cancer resection surgery on tumor recurrence or metastasis.