Miracle-dz/UniFAR-FTUs huggingface dataset:
Cancer-Associated Fibroblasts from Lung Tumors Maintain Their Immunosuppressive Abilities after High-Dose Irradiation

Accumulating evidence supports the notion that high-dose (>5 Gy) radiotherapy (RT) regimens are triggering stronger pro-immunogenic effects than standard low-dose (2 Gy) regimens. However, the effects of RT on certain immunoregulatory elements in tumors remain unexplored. In this study, we have investigated the effects of high-dose radiotherapy (HD-RT) on the immunomodulating functions of cancer-associated fibroblasts (CAFs). Primary CAF cultures were established from lung cancer specimens derived from patients diagnosed for non-small cell lung cancer. Irradiated and non-irradiated CAFs were examined for immunomodulation in experiments with peripheral blood mononuclear cells from random, healthy donors. Regulation of lymphocytes behavior was checked by lymphocyte proliferation assays, lymphocyte migration assays, and T-cell cytokine production. Additionally, CAF-secreted immunoregulatory factors were studied by multiplex protein arrays, ELISAs, and by LC-MS/MS proteomics. In all functional assays, we observed a powerful immunosuppressive effect exerted by CAF-conditioned medium on activated T-cells (p > 0.001), and this effect was sustained after a single radiation dose of 18 Gy. Relevant immunosuppressive molecules such as prostaglandin E2, interleukin-6, and -10, or transforming growth factor-β were found in CAF-conditioned medium, but their secretion was unchanged after irradiation. Finally, immunogenic cell death responses in CAFs were studied by exploring the release of high motility group box-1 and ATP. Both alarmins remained undetectable before and after irradiation. In conclusion, CAFs play a powerful immunosuppressive effect over activated T-cells, and this effect remains unchanged after HD-RT. Importantly, CAFs do not switch on immunogenic cell death responses after exposure to HD-RT.
The Relationship between Proteinuria and Coronary Risk: A Systematic Review and Meta-Analysis

Background Markers of kidney dysfunction such as proteinuria or albuminuria have been reported to be associated with coronary heart disease, but the consistency and strength of any such relationship has not been clearly defined. This lack of clarity has led to great uncertainty as to how proteinuria should be treated in the assessment and management of cardiovascular risk. We therefore undertook a systematic review of published cohort studies aiming to provide a reliable estimate of the strength of association between proteinuria and coronary heart disease. Methods and Findings A meta-analysis of cohort studies was conducted to obtain a summary estimate of the association between measures of proteinuria and coronary risk. MEDLINE and EMBASE were searched for studies reporting an age- or multivariate-adjusted estimate and standard error of the association between proteinuria and coronary heart disease. Studies were excluded if the majority of the study population had known glomerular disease or were the recipients of renal transplants. Two independent researchers extracted the estimates of association between proteinuria (total urinary protein >300 mg/d), microalbuminuria (urinary albumin 30–300 mg/d), macroalbuminuria (urinary albumin >300 mg/d), and risk of coronary disease from individual studies. These estimates were combined using a random-effects model. Sensitivity analyses were conducted to examine possible sources of heterogeneity in effect size. A total of 26 cohort studies were identified involving 169,949 individuals and 7,117 coronary events (27% fatal). The presence of proteinuria was associated with an approximate 50% increase in coronary risk (risk ratio 1.47, 95% confidence interval [CI] 1.23–1.74) after adjustment for known risk factors. For albuminuria, there was evidence of a dose–response relationship: individuals with microalbuminuria were at 50% greater risk of coronary heart disease (risk ratio 1.47, 95% CI 1.30–1.66) than those without; in those with macroalbuminuria the risk was more than doubled (risk ratio 2.17, 1.87–2.52). Sensitivity analysis indicated no important differences in prespecified subgroups. Conclusion These data confirm a strong and continuous association between proteinuria and subsequent risk of coronary heart disease, and suggest that proteinuria should be incorporated into the assessment of an individual's cardiovascular risk.
Kinects and Human Kinetics: A New Approach for Studying Crowd Behavior

Modeling crowd behavior relies on accurate data of pedestrian movements at a high level of detail. Imaging sensors such as cameras provide a good basis for capturing such detailed pedestrian motion data. However, currently available computer vision technologies, when applied to conventional video footage, still cannot automatically unveil accurate motions of groups of people or crowds from the image sequences. We present a novel data collection approach for studying crowd behavior which uses the increasingly popular low-cost sensor Microsoft Kinect. The Kinect captures both standard camera data and a three-dimensional depth map. Our human detection and tracking algorithm is based on agglomerative clustering of depth data captured from an elevated view - in contrast to the lateral view used for gesture recognition in Kinect gaming applications. Our approach transforms local Kinect 3D data to a common world coordinate system in order to stitch together human trajectories from multiple Kinects, which allows for a scalable and flexible capturing area. At a testbed with real-world pedestrian traffic we demonstrate that our approach can provide accurate trajectories from three Kinects with a Pedestrian Detection Rate of up to 94% and a Multiple Object Tracking Precision of 4 cm. Using a comprehensive dataset of 2240 captured human trajectories we calibrate three variations of the Social Force model. The results of our model validations indicate their particular ability to reproduce the observed crowd behavior in microscopic simulations.
Climate Clubs: Can Small Groups of Countries make a Big Difference in Addressing Climate Change?

Clubs, defined as smaller groups of countries that take action outside of the United Nations Framework Convention on Climate Change (UNFCCC), have been suggested in the literature as a way forward for climate action. Some have suggested them as a replacement of the UNFCCC. This article, by contrast, explores how clubs could assist in catalyzing greater ambition, defined as emissions reduction targets in line with climate science, which would eventually be captured in the UNFCCC. An analysis of the existing climate club landscape shows that clubs currently promote dialogue and/or implementation of specific activities. While these clubs make important contributions, their mandate and configuration are not focused on significantly increasing ambition. Current clubs enable incremental, rather than transformational change. An analysis of selected proposals for new kinds of climate clubs shows that, as a common element, they call for further incentives for action to underpin greater ambition. The article further analyzes a set of incentives, predominantly economic, for ‘transformational clubs’, related to trade, investment, labour mobility or access to finance, and identifies a set of future research questions.
Effect of the developmental stage and tissue position on the expression and glycosylation of recombinant glycoprotein GA733-FcK in transgenic plants

The influence of developmental stage and position (top, middle, and base) of leaves and stem tissues on the expression and glycosylation pattern of a recombinant therapeutic protein -GA733-FcK- was observed in transgenic seedlings during a 16-week growth period. RNA expression gradually increased with age in the middle and basal leaves and decreased in top leaves after 14 weeks. The protein expression level at all leaf positions increased until 14 weeks and slightly decreased at 16 weeks; it was lower in yellow leaves than in green leaves. In stem, protein expression gradually decreased from the top to the base. The glycosylation patterns of GA733-FcK were analyzed from 10 to 16 weeks. The plant-specific glycans increased in the top leaves at 14 weeks, but only slightly changed in the middle and basal leaves. The structure of glycans varied with tissue position. The glycosylation level in the top and middle leaves increased until 12 and 14 weeks, respectively, and decreased thereafter, whereas it decreased in basal leaves until 14 weeks and increased at 16 weeks. In stem, all three sections showed high-mannose type glycan structures. The area size of the glycans was significantly higher in the top stem than in both the middle and basal stems, and it was smaller in yellow leaves than in green leaves. The glycan profiles were similar between green and yellow leaves until 16 weeks. Thus, biomass-harvesting time should be optimized to obtain recombinant therapeutic proteins with ideal glycan structure profiles.
Mafia business: The Mafia ethic and the spirit of capitalism

This book is an account both of the old Mafia of the Godfather and of its transformation into a network of gangsters and capitalists today, posing a major threat to democratic politics. The new Mafia combines large-scale business and banking activity with drug dealing, political corruption and widespread violence. Powerful, ruthless and rich, it has convulsed Southern Italy with a spate of murders. Its victims include an MP, a celebrated general, judges and prosecutors, policemen and ordinary citizens. It has turned itself into an entrepreneurial machine of a formidable kind, enjoying advantages denied to ordinary capitalist companies.
Going with the Grain of Cognition: Applying Insights from Psychology to Build Support for Childhood Vaccination

Childhood vaccination is widely considered to be one of the most successful public health interventions. Yet, the effective delivery of vaccination depends upon public willingness to vaccinate. Recently, many countries have faced problems with vaccine hesitancy, where a growing number of parents perceive vaccination to be unsafe or unnecessary, leading some to delay or refuse vaccines for their children. Effective intervention strategies for countering this problem are currently sorely lacking, however. Here, we propose that this may be because existing strategies are grounded more in intuition than insights from psychology. Consequently, such strategies are sometimes at variance with basic psychological principles and assumptions. By going against the grain of cognition, such strategies potentially run the risk of undermining persuasive efforts to reduce vaccine hesitancy. We demonstrate this by drawing on key insights from cognitive and social psychology to show how various known features of human psychology can lead many intuitively appealing intervention strategies to backfire, yielding unintended and undesirable repercussions. We conclude with a summary of potential avenues of investigation that may be more effective in addressing vaccine hesitancy. Our key message is that intervention strategies must be crafted that go with the grain of cognition by incorporating key insights from the psychological sciences.
Effects of phosphorus doping on J-V and C-V characteristics of pulsed laser deposited camphoric carbon/P-silicon heterojunction device

The current density-voltage (J-V) and capacitance voltage (C-V) characteristics of a p-n heterojunction device are studied. The device was fabricated by depositing phosphorus (P) doped carbon (C) thin film on p-type silicon (Si) substrate by pulsed laser deposition (PLD) technique at room temperature. Camphor (C10H16O), a natural source, was used as the starting precursor for the carbon layer of the heterostructure. Carbon layers of the device were obtained using target containing different amount of P. Both the J-V and C-V characteristics reveal that the device behaves as a successful p-n junction device up to a certain P content of the target material for C layer, and this is near about 5% of P by mass. At higher P content of the target, the material properties of the grown C layer on Si change and the device performance deteriorates. The built-in potential of the device with varying P content of the target material for C is also estimated and found them to agree well with the experimentally obtained device characteristics.
The Effect of Relative Flow on the Asymmetric Structure in the Interior of Hurricanes

Abstract Asymmetric structure of tropical cyclones simulated by the Geophysical Fluid Dynamics Laboratory high-resolution triply nested movable-mesh hurricane model was analyzed. Emphasis was placed on the quasi-steady component of the asymmetric structure in the region of the eyewall. It was found that the asymmetry was primarily caused by the relative wind, that is, the flow entering and leaving the storm region relative to the moving storm. A set of idealized numerical experiments was first performed both with a constant and a variable Coriolis parameter ( f ) and the addition of basic flows that were either constant or sheared with height. Analysis was then made for one case of Hurricane Gilbert (1988) to demonstrate that the quasi-steady asymmetric structure analyzed in the idealized studies could be identified in this real data case. Vorticity analysis in the variable f experiment indicated that quasi-steady asymmetries resulted in the eyewall region through the effect of vorticity advection due to .
Don't multiply lightly: Quantifying problems with the acoustic model assumptions in speech recognition

We describe a series of experiments simulating data from the standard Hidden Markov Model (HMM) framework used for speech recognition. Starting with a set of test transcriptions, we begin by simulating every step of the generative process. In each subsequent experiment, we substitute a real component for a simulated component (real state durations rather than simulating from the transition models, for example), and compare the word error rates of the resulting data, thus quantifying the relative costs of each modeling assumption. A novel sampling process allows us to test the independence assumptions of the HMM, which appear to present far more serious problems than the other data/model mismatches.
STABILITY ANALYSIS FOR SYSTEMS WITH LARGE DELAY PERIOD : A SWITCHING METHOD

This paper studies an exponential stability problem for a class of timevarying delay systems with large delay period. The time-varying delay is interval-range. Although large delay period (LDP) is often present in practical control systems, the problems of stability analysis for such systems have been unsolved to date. In this paper, a new method based on switching technique is proposed to solve the case of LDP. It addresses how long and how frequent the LDP can be and still maintain the system exponentially stable. We first utilize switched delay systems, which may include an unstable subsystem, to model such a system. Then, the concepts of frequency and length rate of LDP are introduced. Next, based on a novel piecewise Lyapunov functional including the largedelay-integral terms (LDITs), sufficient conditions guaranteeing exponential stability are developed. Without LDP, the criterion obtained in this paper contains results already published as a special case. Two numerical examples are given to show the effectiveness of the proposed method.
Where is the problem of “Where is the mind?”?

We propose that the discussions about “where the mind is” depend directly on the metaphysical preconception and definition of “mind”. If we see the mind from one perspective (individualist), it will be only in the brain, and if we see it from another (active externalist), it will be embedded in the body and extended into the world. The “whereabouts” of the mind depends on our 1 of mind. Therefore, we should not ask if the mind is somewhere, but if it is somehow.
Laying the Foundations for a Human-Predator Conflict Solution: Assessing the Impact of Bonelli's Eagle on Rabbits and Partridges

Background Predation may potentially lead to negative effects on both prey (directly via predators) and predators (indirectly via human persecution). Predation pressure studies are, therefore, of major interest in the fields of theoretical knowledge and conservation of prey or predator species, with wide ramifications and profound implications in human-wildlife conflicts. However, detailed works on this issue in highly valuable –in conservation terms– Mediterranean ecosystems are virtually absent. This paper explores the predator-hunting conflict by examining a paradigmatic, Mediterranean-wide (endangered) predator-two prey (small game) system. Methodology/Principal Findings We estimated the predation impact (‘kill rate’ and ‘predation rate’, i.e., number of prey and proportion of the prey population eaten, respectively) of Bonelli's eagle Aquila fasciata on rabbit Oryctolagus cuniculus and red-legged partridge Alectoris rufa populations in two seasons (the eagle's breeding and non-breeding periods, 100 days each) in SE Spain. The mean estimated kill rate by the seven eagle reproductive units in the study area was c. 304 rabbits and c. 262 partridges in the breeding season, and c. 237 rabbits and c. 121 partridges in the non-breeding period. This resulted in very low predation rates (range: 0.3–2.5%) for both prey and seasons. Conclusions/Significance The potential role of Bonelli's eagles as a limiting factor for rabbits and partridges at the population scale was very poor. The conflict between game profitability and conservation interest of either prey or predators is apparently very localised, and eagles, quarry species and game interests seem compatible in most of the study area. Currently, both the persecution and negative perception of Bonelli's eagle (the ‘partridge-eating eagle’ in Spanish) have a null theoretical basis in most of this area.
α-Synuclein Expression Selectively Affects Tumorigenesis in Mice Modeling Parkinson's Disease

Alpha Synuclein (α-Syn) is a protein implicated in mechanisms of neuronal degeneration in Parkinson's disease (PD). α-Syn is primarily a neuronal protein, however, its expression is found in various tumors including ovarian, colorectal and melanoma tumors. It has been hypothesized that neurodegeneration may share common mechanisms with oncogenesis. We tested whether α-Syn expression affects tumorigenesis of three types of tumors. Specifically, B16 melanoma, E0771 mammary gland adenocarcinoma and D122 Lewis lung carcinoma. For this aim, we utilized transgenic mice expression the human A53T α-Syn form. We found that the in vivo growth of B16 and E0771 but not D122 was enhanced in the A53T α-Syn mice. The effect on tumorigenesis was not detected in age-matched APP/PS1 mice, modeling Alzheimer's disease (AD), suggesting a specific effect for α-Syn- dependent neurodegeneration. Importantly, transgenic α-Syn expression was detected within the three tumor types. We further show uptake of exogenously added, purified α-Syn, by the cultured tumor cells. In accord, with the affected tumorigenesis in the young A53T α-Syn mice, over- expression of α-Syn in cultured B16 and E0771 cells enhanced proliferation, however, had no effect on the proliferation of D122 cells. Based on these results, we suggest that certain forms of α-Syn may selectively accelerate cellular mechanisms leading to cancer.
Selecting Critical Patterns Based on Local Geometrical and Statistical Information

Pattern selection methods have been traditionally developed with a dependency on a specific classifier. In contrast, this paper presents a method that selects critical patterns deemed to carry essential information applicable to train those types of classifiers which require spatial information of the training data set. Critical patterns include those edge patterns that define the boundary and those border patterns that separate classes. The proposed method selects patterns from a new perspective, primarily based on their location in input space. It determines class edge patterns with the assistance of the approximated tangent hyperplane of a class surface. It also identifies border patterns between classes using local probability. The proposed method is evaluated on benchmark problems using popular classifiers, including multilayer perceptrons, radial basis functions, support vector machines, and nearest neighbors. The proposed approach is also compared with four state-of-the-art approaches and it is shown to provide similar but more consistent accuracy from a reduced data set. Experimental results demonstrate that it selects patterns sufficient to represent class boundary and to preserve the decision surface.
RelA-Induced Interferon Response Negatively Regulates Proliferation

Both oncogenic and tumor-suppressor activities are attributed to the Nuclear Factor kappa B (NF-kB) pathway. Moreover, NF-kB may positively or negatively regulate proliferation. The molecular determinants of these opposing roles of NF-kB are unclear. Using primary human mammary epithelial cells (HMEC) as a model, we show that increased RelA levels and consequent increase in basal transcriptional activity of RelA induces IRF1, a target gene. Induced IRF1 upregulates STAT1 and IRF7, and in consort, these factors induce the expression of interferon response genes. Activation of the interferon pathway down-regulates CDK4 and up-regulates p27 resulting in Rb hypo-phosphorylation and cell cycle arrest. Stimulation of HMEC with IFN-γ elicits similar phenotypic and molecular changes suggesting that basal activity of RelA and IFN-γ converge on IRF1 to regulate proliferation. The anti-proliferative RelA-IRF1-CDK4 signaling axis is retained in ER+/HER2- breast tumors analyzed by The Cancer Genome Atlas (TCGA). Using immuno-histochemical analysis of breast tumors, we confirm the negative correlation between RelA levels and proliferation rate in ER+/HER2- breast tumors. These findings attribute an anti-proliferative tumor-suppressor role to basal RelA activity. Inactivation of Rb, down-regulation of RelA or IRF1, or upregulation of CDK4 or IRF2 rescues the RelA-IRF1-CDK4 induced proliferation arrest in HMEC and are points of disruption in aggressive tumors. Activity of the RelA-IRF1-CDK4 axis may explain favorable response to CDK4/6 inhibition observed in patients with ER+ Rb competent tumors.