Miracle-dz/UniFAR-FTUs huggingface dataset:
Heinrich events show two-stage climate response in transient glacial simulations, Climate of the Past, in open review, doi: 10.5194/cp-2018-16

Heinrich events are among the dominant modes of glacial climate variability. During these events, massive iceberg armadas were released by the Laurentide Ice Sheet and sailed across the Atlantic where they melted and released freshwater, as well as detritus, that formed characteristic layers on the seafloor. Heinrich events are known for cold climates in the North Atlantic region and global climate changes. We study these events in a fully coupled complex ice sheet–climate model with synchronous coupling between ice sheets and oceans. The ice discharges occur as an internal variability of the model with a recurrence period of 5 kyr, an event duration of 1–1.5 kyr, and a peak discharge rate of about 50 mSv, roughly consistent with reconstructions. The climate response shows a two-stage behavior, with freshwater release effects dominating the surge phase and ice sheet elevation effects dominating the post-surge phase. As a direct response to the freshwater discharge during the surge phase, deepwater formation in the North Atlantic decreases and the North Atlantic deepwater cell weakens by 3.5 Sv. With the reduced oceanic heat transport, the surface temperatures across the North Atlantic decrease, and the associated reduction in evaporation causes a drying in Europe. The ice discharge lowers the surface elevation in the Hudson Bay area and thus leads to increased precipitation and accelerated ice sheet regrowth in the post-surge phase. Furthermore, the jet stream widens to the north, which contributes to a weakening of the subpolar gyre and a continued cooling over Europe even after the ice discharge. This two-stage behavior can explain previously contradicting model results and understandings of Heinrich events.
Perception and information.

INTRODUCTION . __ . 62 His torical Roo ts . 62 Mapping. Inference . Struc ture . and Mea surement . 62 STRUCTU.RE FROM EXPERIENCE . 64 Informa tion in Fre quency of Occurrence . 64 STRUCTURE FROM CONSTRAINTS. 65 Informa ti on from Bi ts to Simplicity 65 Information from Group Theo ry . 66 STRUCTURE FROM STATISTICS. 67 Informa tion in Tex ture Shape . 67 Information in Do tted Form s . 69 STRUCTURE FROM NEURAL ANALySIS . 70 Information in Fourier Componen ts . 70 STRUCTURE FROM GEOMETRy. 7 1 Information . Geometry . and Sta tic Form . 71 Information . Ge ome try. and Motion . 72 Information for P ercepti on and Acti on . 75 Informa tion. Topology . and the "Geome try of the Visibles" 75 INFORMATION AND ICONIC MEMORy . 76 INFORMATION IN NONVISUAL MODALITIES 77 INFORMATION USE. 77 Equi valence . Cogni tive Pene trabili ty. and Choice . 77 Additivity. Integration . and Multimodal Percep tion. 78 Informa tive Displays 79
Coassembly of synthetic segments of shaker K+ channel within phospholipid membranes.

Increasing evidence suggests that membrane-embedded hydrophobic segments can interact within the phospholipid milieu of the membrane with varying degrees of specificity and thus contribute to the folding and oligomerization of proteins. We have used synthetic peptides corresponding to segments from the hydrophobic core of the Shaker potassium channel as a model system to study interactions between membrane-embedded segments. Three synthetic segments of the Shaker K+ channel, comprising the hydrophobic S2, S3, and S4 sequences, were used, and their secondary structure, their interactions with, and orientation within phospholipid membranes were examined. Secondary structure studies revealed that though S3 and S4 both adopt certain fractions of alpha-helical structures in membrane mimetic environments, the alpha-helical content of S3 is lower. Both S3 and S4 bind strongly to zwitterionic phospholipids, with partition coefficients in the order of 10(4) and 10(5) M-1. ATR-FTIR studies showed that while the S4 peptide is oriented parallel to the membrane surface, S3 tends to a more transmembranal orientation. Enzymatic cleavage experiments demonstrated that the presence of S3 induces some change in the proteolytic accessibility of the S4 segment. Resonance energy transfer measurements, done in high lipid/peptide molar ratios, revealed that S3 and S4 cannot self-associate in zwitterionic phospholipid vesicles but can associate with each other and with the S2 segment of the channel. Furthermore, S3 does not interact with the homologous S4 region from the first repeat of the eel sodium channel, demonstrating specificity in the interactions. These results are in line with data indicating that functionally important interactions indeed exist between the negatively charged S2 and S3 regions and the positively charged S4 region [Papazian, D. M. , et al (1995) Neuron 14, 1293-1301; Planells-Cases, R. , et al. (1994) Proc. Natl. Acad. Sci. U.S.A. 92, 9422-9426]. From a broader point of view, these results provide further support to the notion that interactions (either specific or nonspecific) may exist between transmembrane segments of integral membrane proteins and therefore can contribute to their assembly and organization.
Cysteinyl Leukotriene 1 Receptors as Novel Mechanosensors Mediating Myogenic Tone Together With Angiotensin II Type 1 Receptors—Brief Report

Objective—Myogenic vasoconstriction is mediated by vascular smooth muscle cells of resistance arteries sensing mechanical stretch. Angiotensin II AT1 receptors and in particular AT1BRs in murine vascular smooth muscle cells have been characterized as mechanosensors that cannot fully account for myogenic vasoconstriction observed. Therefore, we aimed at uncovering novel vascular mechanosensors by expression profiling and functional characterization of candidate proteins. Approach and Results—Analyzing myogenic tone of isolated murine mesenteric arteries of AT1A and AT1B receptor double gene-deficient (AT1A/1B−/−) mice ex vivo, we observed a decreased myogenic tone at high intraluminal pressures and an unexpected hyper-reactivity at low intraluminal pressures because of upregulation of cysteinyl leukotriene 1 receptors (CysLT1Rs). Pharmacological blockade of CysLT1Rs with pranlukast significantly reduced myogenic tone not only in AT1A/1B−/− but also in wild-type arteries. In wild-type arteries, additional blockade of angiotensin II AT1 receptors with candesartan resulted in an additive reduction of myogenic tone. Furthermore, calcium imaging experiments were performed with fura-2–loaded human embryonic kidney 293 cells overexpressing CysLT1Rs and with isolated mesenteric vascular smooth muscle cells. Hypo-osmotically induced membrane stretch provoked calcium transients that were significantly reduced by pranlukast. Incubations of isolated mesenteric vascular smooth muscle cells with the 5-lipoxygenase inhibitor zileuton had no effect. Furthermore, the Gq/11-protein inhibitor YM 254890 profoundly reduced myogenic tone to the same extent as induced by the application of pranlukast plus candesartan. Conclusions—Here, we identify a novel, hitherto unappreciated role of CysLT1Rs in vascular regulation. We identified CysLT1Rs as novel mechanosensors in the vasculature involved in myogenic vasoconstriction. Moreover, our findings suggest that myogenic tone is determined by AT1 and CysLT1 receptors acting together as mechanosensors via Gq/11-protein activation.
Atmospheric Oxygen Tension Slows Myoblast Proliferation via Mitochondrial Activation

Background Mitochondrial activity inhibits proliferation and is required for differentiation of myoblasts. Myoblast proliferation is also inhibited by the ∼20% oxygen level used in standard tissue culture. We hypothesize that mitochondrial activity would be greater at hyperoxia (20% O2) relative to more physiological oxygen (5% O2). Methodology/Principal Findings Murine primary myoblasts from isolated myofibres and conditionally immortalized H-2K myoblasts were cultured at 5% and 20% oxygen. Proliferation, assayed by cell counts, EdU labeling, and CFSE dilution, was slower at 20% oxygen. Expression of MyoD in primary myoblasts was delayed at 20% oxygen, but myogenicity, as measured by fusion index, was slightly higher. FACS-based measurement of mitochondrial activity indicators and luminometric measurement of ATP levels revealed that mitochondria exhibited greater membrane potential and higher levels of Reactive Oxygen Species (ROS) at 20% oxygen with concomitant elevation of intracellular ATP. Mitochondrial mass was unaffected. Low concentrations of CCCP, a respiratory chain uncoupler, and Oligomycin A, an ATP synthase inhibitor, each increased the rate of myoblast proliferation. ROS were investigated as a potential mechanism of mitochondrial retrograde signaling, but scavenging of ROS levels by N-acetyl-cysteine (NAC) or α-Phenyl-N-tert-butylnitrone (PBN) did not rescue the suppressed rate of cell division in hyperoxic conditions, suggesting other pathways. Primary myoblasts from older mice showed a slower proliferation than those from younger adult mice at 20% oxygen but no difference at 5% oxygen. Conclusions/Significance These results implicate mitochondrial regulation as a mechanistic explanation for myoblast response to oxygen tension. The rescue of proliferation rate in myoblasts of aged mice by 5% oxygen suggests a major artefactual component to age-related decline of satellite cell proliferation in standard tissue culture at 20% oxygen. It lends weight to the idea that these age-related changes result at least in part from environmental factors rather than characteristics intrinsic to the satellite cell.
Comparative In Vitro Pharmacodynamics of Caspofungin, Micafungin, and Anidulafungin against Germinated and Nongerminated Aspergillus Conidia

ABSTRACT The concentration-dependent effects of echinocandins on the metabolic activity of Aspergillus spp. were comparatively studied by using nongerminated and germinated conidia. The susceptibilities of 11 Aspergillus fumigatus, 8 A. terreus and 8 A. flavus isolates to caspofungin, micafungin, and anidulafungin were studied by a CLSI (formerly NCCLS) M38-A broth microdilution-based method. After 48 h of incubation the minimum effective concentration (MEC) was defined microscopically. Metabolic activity was assessed by the 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide assay and modeled by using the sigmoid (Emax) or “bell-shaped” model. The median MEC values of caspofungin (0.5 to 1 μg/ml), micafungin (0.06 to 0.12 μg/ml), and anidulafungin (0.03 μg/ml) against nongerminated conidia increased by 0 to 1, 1 to 2, and 2 to 3 twofold dilutions, respectively (depending on the species), over those against germinated conidia. A similar shift to the right was demonstrated for the corresponding curves of metabolic activity. There was a significant correlation between the degrees of maximal metabolic inhibition caused by different echinocandins at both the species level (greater inhibition for A. flavus) and the strain level (r = 0.84 to 0.93; P < 0.0001). Paradoxical increases in metabolism in the presence of higher concentrations of caspofungin, micafungin, and anidulafungin were detected in 6, 2, and 5 of the A. fumigatus isolates, respectively; 5, 1, and 2 of the A. terreus isolates, respectively; and 1, 0, and 0 of the A. flavus isolates, respectively. Based on the model, 50% of the maximal paradoxical increase was detected with 4.2, 11.1, and 10.8 μg/ml of caspofungin, micafungin, and anidulafungin, respectively. All echinocandins therefore exerted comparable levels of maximal metabolic inhibition against Aspergillus spp. at concentrations that were differentially increased for germinated versus nongerminated conidia. The paradoxical increase in metabolism occurred more frequently and at lower concentrations with caspofungin than with micafungin and anidulafungin.
Reduced Venous Compliance in Young Women with Type 1 Diabetes – Further Aggravated by Prolonged Elevated Levels of HbA1c

Background Young patients with diabetes present with reduced compensatory responses to hypovolemic stress. Less compliant veins could be a contributing factor, since roughly two-thirds of the blood volume resides in the venous system as a blood reservoir, adjusting proper venous inflow to the heart. The aim of this study was to measure venous compliance and lower limb blood pooling during hypovolemic stress, and to correlate them to indices of diabetes severity and glucose control. Methods Fifteen young women with type 1 diabetes (DW) and 18 healthy age-matched women (C) were subjected to lower body negative pressure (LBNP) (11–44 mmHg), creating hypovolemic stress. Lower limb blood pooling was measured with strain gage technique and venous compliance calculated as the relationship between ∆V/∆P. Results DW presented with reduced blood pooling (e.g., blood pooling during LBNP of 44 mmHg, DW, 1.69 ± 0.10; C, 2.10 ± 0.08 (ml/100 ml), and P = 0.003). Calculated venous compliance was also reduced in DW (e.g., compliance at 20 mmHg, DW, 0.046 ± 0.003; C, 0.059 ± 0.002 (ml/100 ml/mmHg), and P = 0.002). A progressive reduction in both venous compliance (P < 0.007) and blood pooling (P < 0.005) was seen with increasing level of HbA1c, and furthermore, less strongly associated with presence of microvascular disease (signs of retinopathy). Conclusion Women with type 1 diabetes present with both reduced venous compliance and blood pooling. The reductions were particularly present in patients with long-standing poor glycemic control.
Clinical Ophthalmology Dovepress

hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms Comparison of intraocular pressure adjusted by central corneal thickness or corneal biomechanical properties as measured in glaucomatous eyes using noncontact tonometers and the goldmann applanation tonometer Purpose: To investigate the correlation coefficients between intraocular pressure (IOP) before and after adjusting for central corneal thickness (CCT) and corneal biomechanical properties. Patients and methods: A total of 218 eyes of 218 patients with primary open-angle glaucoma (mean age =71.5 years; mean spherical equivalent =−0.51 D; mean deviation determined by Humphrey visual field analyzer =−3.22 dB) were included in this study. The tIOP and tIOPCCT, which were adjusted by the CCT (with tIOP meaning IOP not adjusted by CCT, as determined using the CT-1P; and tIOPCCT meaning IOP adjusted by CCT, as determined using the CT-1P), were determined using a noncontact tonometer. The IOPg and IOPCCT, which were adjusted by CCT, and IOPcc adjusted by corneal biomechanical properties were determined using a Reichert 7CR (with IOPg meaning IOP not adjusted by CCT or corneal biomechanical properties, as determined using the Reichert 7CR; IOPCCT meaning IOP adjusted by CCT, as determined using the Reichert 7CR; and IOPcc meaning IOP adjusted by corneal biomechanical properties, as determined using the Reichert 7CR). The GT and GTCCT adjusted by CCT were determined using a Goldmann applanation tonometer (with GT meaning IOP not adjusted by CCT, as determined using the Goldmann applanation tonometer; and with GTCCT meaning IOP adjusted by CCT, as determined using the GAT). Pearson's correlation coefficients among the IOPs were calculated and compared. P-values ,0.05 were considered as statistically significant. (mean ± standard deviation), respectively. The correlation coefficient between tIOPCCT and tIOP (r=0.979) was significantly higher than that between tIOPCCT and the other IOPs (r=0.668–0.852; P,0.001, respectively). The correlation coefficient between IOPCCT and IOPg (r=0.994) or IOPcc and IOPg (r=0.892) was significantly higher than that between IOPCCT or IOPcc and the other IOPs (r=0.669–0.740; P,0.001, respectively). The correlation coefficient between GTCCT and GT (r=0.989) was significantly higher than that between GTCCT and the other IOPs (r=0.669–0.740; P,0.001, respectively). Conclusion: The IOP adjusted by CCT or corneal biomechanical properties depends on the measurement instrument itself, rather than the adjustment methods, for eyes of …
The Unique Contributions of Perceiver and Target Characteristics in Person Perception

Models of person perception have long asserted that our impressions of others are guided by characteristics of both the target and perceiver. However, research has not yet quantified to what extent perceivers and targets contribute to different impressions. This quantification is theoretically critical, as it addresses how much an impression arises from “our minds” versus “others’ faces. ” Here, we apply cross-classified random effects models to address this fundamental question in social cognition, using approximately 700,000 ratings of faces. With this approach, we demonstrate that (a) different trait impressions have unique causal processes, meaning that some impressions are largely informed by perceiver-level characteristics whereas others are driven more by physical target-level characteristics; (b) modeling of perceiver- and target-variance in impressions informs fundamental models of social perception; (c) Perceiver × Target interactions explain a substantial portion of variance in impressions; (d) greater emotional intensity in stimuli decreases the influence of the perceiver; and (e) more variable, naturalistic stimuli increases variation across perceivers. Important overarching patterns emerged. Broadly, traits and dimensions representing inferences of character (e.g., dominance) are driven more by perceiver characteristics than those representing appearance-based appraisals (e.g., youthful-attractiveness). Moreover, inferences made of more ambiguous traits (e.g., creative) or displays (e.g., faces with less extreme emotions, less-controlled stimuli) are similarly driven more by perceiver than target characteristics. Together, results highlight the large role that perceiver and target variability play in trait impressions, and develop a new topography of trait impressions that considers the source of the impression.
Prevalence of parameter indicators of obesity and its relationship with metabolic syndrome in urban Moroccan women

This study aimed to examine the relationship between metabolic syndrome (MS) and different types of obesity in urban Moroccan women. On 213 women aged 25–55 years, Triglycerides (TG), total cholesterol, high‐density lipoprotein cholesterol (HDL‐c), lower‐density lipoprotein cholesterol (LDL‐c), and fasting blood glucose levels were assessed. Body mass index (BMI), waist to hip ratio (WHR), Waist circumference (WC), and blood pressure (BP) were also measured. Globally 36.6% of women were overweight (25 ≤ BMI < 30 m2), 23.9% obese (BMI > 30 m2), 19.7% had WHR > 0.85 and 28.8% had WC ≥ 88 cm. Indicators of obesity increased with age and the prevalence of co‐morbid factors increased with obesity. The women with android obesity (WHR > 0.85) and central obesity (WC ≥ 88 cm) had greater risk compared to those with overweight and general obesity. The prevalence of MS was 17.8% and increased (31.49%) with high BMI and high WHR (50%). MS and its co‐morbidity factors are prevalent among Moroccan women aged 35years and over. The exaggerated influence of obesity in this prevalence suggests that the prevention of obesity could prevent MS and its complications. Am. J. Hum. Biol., 2008. © 2008 Wiley‐Liss, Inc.
CD152 (CTLA-4) Determines the Unequal Resistance of Th1 and Th2 Cells against Activation-induced Cell Death by a Mechanism Requiring PI3 Kinase Function

Survival of antigen-experienced T cells is essential for the generation of adaptive immune responses. Here, we show that the genetic and antibody-mediated inactivation of CD152 (cytotoxic T lymphocyte antigen 4) in T helper (Th) effector cells reduced the frequency of nonapoptotic cells in a completely Fas/Fas ligand (FasL)–dependent manner. CD152 cross-linking together with stimulation of CD3 and CD28 on activated Th2 cells prevented activation-induced cell death (AICD) as a result of reduced Fas and FasL expression. Apoptosis protection conferred by CD152 correlated with the up-regulation of Bcl-2 and was mediated by phosphatidylinositol 3 kinase, which prevented FasL expression through the inhibitory phosphorylation of Forkhead transcription factor FKHRL1. We show that signals induced by CD152 act directly on activated T lymphocytes and, due to its differential surface expression on activated Th1 and Th2 cells, induce resistance to AICD mainly in Th2 cells.
Mechanisms of action and rationale for the use of checkpoint inhibitors in cancer

The large family of costimulatory molecules plays a crucial role in regulation of the immune response. These molecules modulate TCR signalling via phosphorylation cascades. Some of the coinhibitory members of this family, such as PD-1 and CTLA-4, already constitute approved targets in cancer therapy and, since 2011, have opened a new area of antitumour immunotherapy. Many antibodies targeting other inhibitory receptors (Tim-3, VISTA, Lag-3 and so on) or activating costimulatory molecules (OX40, GITR and so on) are under evaluation. These antibodies have multiple mechanisms of action. At the cellular level, these antibodies restore the activation signalling pathway and reprogram T cell metabolism. Tumour cells become resistant to apoptosis when an intracellular PD-L1 signalling is blocked. CD8+ T cells are considered to be the main effectors of the blockade of inhibitory receptors. Certain CD8+ T cell subsets, such as non-hyperexhausted (CD28+, T-bethigh, PD-1int), follicular-like (CXCR-5+) or resident memory CD8+ T cells, are more prone to be reactivated by anti-PD-1/PD-L1 monoclonal antibody (mAb). In the future, the challenge will be to rationally combine drugs able to make the tumour microenvironment more permissive to immunotherapy in order to potentiate its clinical activity.
Active Learning Efficiency Benchmark for Coreference Resolution Including Advanced Uncertainty Representations

Active learning is a powerful technique that accelerates model learning by iteratively expanding training data based on the model's feedback. This approach has proven particularly relevant in natural language processing and other machine learning domains. While active learning has been extensively studied for conventional classification tasks, its application to more specialized tasks like neural coreference resolution has the potential for improvement. In our research, we present a significant advancement by applying active learning to the neural coreference problem, and setting a benchmark of 39 % reduction in required annotations for training data. Simultaneously, it preserves performance compared to the original model trained on the full data. We compare various uncertainty sampling techniques along with Bayesian modifications of coreference resolution models, conducting a comprehensive analysis of annotation efforts. The results demonstrate that the best-performing techniques seek to maximize label annotation in previously chosen documents, showcasing their effectiveness and preserving performance.
Content based Image Retrieval using Combined Features

Based Image Retrieval is the application of computer vision techniques to the image retrieval problem of searching for digital images in large databases. The method of CBIR discussed in this paper can filter images based their content and would provide a better indexing and return more accurate results. In this paper techniques to retrieve image based on their content namely color, texture and combined retrieval using both the features together. Combined feature retrieval gives better and more accurate result as compared to using a single technique for retrieval.