Miracle-dz/UniFAR-FTUs huggingface dataset:
Primary Human Blood Dendritic Cells for Cancer Immunotherapy—Tailoring the Immune Response by Dendritic Cell Maturation

Dendritic cell (DC)-based cancer vaccines hold the great promise of tipping the balance from tolerance of the tumor to rejection. In the last two decades, we have gained tremendous knowledge about DC-based cancer vaccines. The maturation of DCs has proven indispensable to induce immunogenic T cell responses. We review the insights gained from the development of maturation cocktails in monocyte derived DC-based trials. More recently, we have also gained insights into the functional specialization of primary human blood DC subsets. In peripheral human blood, we can distinguish at least three primary DC subsets, namely CD1c+ and CD141+ myeloid DCs and plasmacytoid DCs. We reflect the current knowledge on maturation and T helper polarization by these blood DC subsets in the context of DC-based cancer vaccines. The maturation stimulus in combination with the DC subset will determine the type of T cell response that is induced. First trials with these natural DCs underline their excellent in vivo functioning and mark them as promising tools for future vaccination strategies.
Intensive gait training in toddlers with cerebral palsy: A pilot study

Background: Reduced muscle growth may be involved in the development of contractures in children with cerebral palsy (CP). Here, we report data from a pilot study of intensive gait training in CP toddlers. Methods: Five children with CP aged 8-30 months performed activity-based gait training for one hour/day, five days/week for three consecutive months. Included children were diagnosed with spastic CP, had a Gross Motor Function Classification System (GMFCS) score of I–II, and were not epileptic. All children wore pedometers during training. Before and after the training period, kinematic and qualitative gait analysis, clinical and objective evaluation of spasticity, Gross Motor Function Measure-66 (GMFM-66), and ultrasound of the affected medial gastrocnemius (MG) muscle were performed. Two children were also tested before and after three months of receiving only standard care (SC). Results: On average 1410 steps/session were logged during 63 days of training. More steps were achieved at home than at a central facility. During training, MG muscle volume increased significantly, while it decreased for SC children. Gait improved qualitatively in all children, and GMFM-66 score improved in four of the five children. Similar improvements were seen among the SC children. Two children had pathologically increased muscle stiffness prior to training, which was reduced during training. Reflex stiffness was unchanged in all five children. Conclusions: This pilot study suggests that intensive gait training may increase muscle volume, improve walking skills and reduce passive muscle stiffness in toddlers with CP.
Th1 Cytokines Facilitate CD8-T-Cell-Mediated Early Resistance to Infection with Mycobacterium tuberculosis in Old Mice

ABSTRACT Numerous immunological defects begin to emerge as an individual ages, the consequence of which is heightened susceptibility to infectious diseases. Despite this decline in immune function, old mice display an early transient resistance to Mycobacterium tuberculosis infection in the lung, which is dependent on CD8 T cells and gamma interferon (IFN-γ) production. In this study, we investigated the mechanism of resistance by examining the CD8-T-cell phenotype and function in old naïve and M. tuberculosis-infected mice. Pulmonary CD8 T cells from naïve old mice expressed cell surface markers of memory in addition to receptors for several Th1 cytokines. Stimulation of lung cells from naïve old mice with a combination of Th1 cytokines (interleukin-2 [IL-2], IL-12, and IL-18) resulted in nonspecific production of IFN-γ by memory CD8 T cells. Following aerosol infection with M. tuberculosis, the lungs of old mice contained significantly more IL-12, IL-18, and IFN-γ than the lungs of young mice contained. Together, these data demonstrate that the increased and early production of Th1 cytokines in the lungs of M. tuberculosis-infected old mice, in combination with CD8 T cells that can nonspecifically produce IFN-γ, leads to transient control of M. tuberculosis growth in the lungs of old mice. Further characterization of this mechanism should provide essential information regarding the aging immune system and should contribute to the development of novel strategies to decrease the morbidity and mortality of the aging population associated with infectious diseases.
A critique of the socio-spatial debate and the publicness of urban space

ABSTRACT Research on urban processes under capitalism and the resulting transformations of urban space is caught in a socio-spatial dualistic debate, which neglects the continuum and relativities of space. The author aims to extend this debate through an in-depth review and critique of the main perspectives on socio-spatial relations. He argues that in capitalist urban processes urban space plays a dual role as both the public sphere and arena of capital accumulation. However, importantly, this dual role has led to the multidimensional nature of the publicness of space which, in turn, collaboratively results in increasingly blurred boundaries between ‘public’ and ‘private’ in cities. To grapple with the new features of urban space for theory and empirical research, the article offers an alternative property rights approach. Rather than treating space as monolithic, the proposed property rights approach puts the case for analysing space as a continuum. On this basis, the author discusses how that approach can be used for empirical research.
Immunohistochemical detection of a potential molecular therapeutic target for canine hemangiosarcoma

Canine hemangiosarcoma (HSA) is a progressive malignant neoplasm of dogs for which there is currently no effective treatment. A recent study suggested that receptor tyrosine kinases (RTKs), the PI3K/Akt/m-TOR and MAPK pathways are all activated in canine and human HSA. The aim of the present study was to investigate the overexpression of these proteins by immunohistochemistry in canine splenic HSA to identify potential molecular therapeutic targets. A total of 10 splenic HSAs and two normal splenic samples surgically resected from dogs were sectioned and stained with hematoxylin and eosin for histological diagnosis or analyzed using immunohistochemistry. The expression of RTKs, c-kit, VEGFR-2 and PDGFR-2, as well as PI3K/Akt/m-TOR and MEK was higher in canine splenic HSAs compared to normal spleens. These proteins may therefore be potential therapeutic targets in canine splenic HSA.
PML induces compaction, TRF2 depletion and DNA damage signaling at telomeres and promotes their alternative lengthening

ABSTRACT The alternative lengthening of telomeres (ALT) mechanism allows cancer cells to escape senescence and apoptosis in the absence of active telomerase. A characteristic feature of this pathway is the assembly of ALT-associated promyelocytic leukemia (PML) nuclear bodies (APBs) at telomeres. Here, we dissected the role of APBs in a human ALT cell line by performing an RNA interference screen using an automated 3D fluorescence microscopy platform and advanced 3D image analysis. We identified 29 proteins that affected APB formation, which included proteins involved in telomere and chromatin organization, protein sumoylation and DNA repair. By integrating and extending these findings, we found that APB formation induced clustering of telomere repeats, telomere compaction and concomitant depletion of the shelterin protein TRF2 (also known as TERF2). These APB-dependent changes correlated with the induction of a DNA damage response at telomeres in APBs as evident by a strong enrichment of the phosphorylated form of the ataxia telangiectasia mutated (ATM) kinase. Accordingly, we propose that APBs promote telomere maintenance by inducing a DNA damage response in ALT-positive tumor cells through changing the telomeric chromatin state to trigger ATM phosphorylation.
Abnormal Pregnancy Sonogram: Selective Indication for Fetal Karyotype

The inability to make a definitive diagnosis in the fetus with a sonographically identified abnormality often results in parental and physician uncertainty. An antenatal chromosome evaluation could resolve this uncertainty. Forty-one fetuses with an abnormal ultrasound examination were tested for karyotypic abnormality using a variety of specimens. Nearly one-third (13 of 41) of these featuses had various chromosome abnormalities. There were only seven survivors in this series, underscoring the often poor prognosis when a significant ultrasound defect is detected antenatally. Knowledge of the fetal chromosome constitution in the setting of an abnormal ultrasound has important epidemiologic, cost-benefit, counseling, and pregnancy management implications.
Development and Validation of a Novel Radiosensitivity Signature in Human Breast Cancer

Purpose: An unmet clinical need in breast cancer management is the accurate identification of patients who will benefit from adjuvant radiotherapy. We hypothesized that integration of postradiation clonogenic survival data with gene expression data across breast cancer cell (BCC) lines would generate a radiation sensitivity signature (RSS) and identify patients with tumors refractive to conventional therapy. Experimental Design: Using clonogenic survival assays, we identified the surviving fraction (SF-2Gy) after radiation across a range of BCC lines. Intrinsic radiosensitivity was correlated to gene expression using Spearman correlation. Functional analysis was performed in vitro, and enriched biologic concepts were identified. The RSS was generated using a Random Forest model and was refined, cross-validated, and independently validated in additional breast cancer datasets. Results: Clonogenic survival identifies a range of radiosensitivity in human BCC lines (SF-2Gy 77%-17%) with no significant correlation to the intrinsic breast cancer subtypes. One hundred forty-seven genes were correlated with radiosensitivity. Functional analysis of RSS genes identifies previously unreported radioresistance-associated genes. RSS was trained, cross-validated, and further refined to 51 genes that were enriched for concepts involving cell-cycle arrest and DNA damage response. RSS was validated in an independent dataset and was the most significant factor in predicting local recurrence on multivariate analysis, outperfoming all clinically used clinicopathologic features. Conclusions: We derive a human breast cancer–specific RSS with biologic relevance and validate this signature for prediction of locoregional recurrence. By identifying patients with tumors refractory to standard radiation this signature has the potential to allow for personalization of radiotherapy. Clin Cancer Res; 21(16); 3667–77. ©2015 AACR.
A classification approach to reconstruct local daily drying dynamics at headwater streams

Headwater streams (HSs) are generally naturally prone to flow intermittence. These intermittent rivers and ephemeral streams have recently seen a marked increase in interest, especially to assess the impact of drying on aquatic ecosystems. The two objectives of this work are (a) to identify the main drivers of flow intermittence dynamics in HS and (b) to reconstruct local daily drying dynamics. Discrete flow states—“flowing” versus “drying”—are modelled as functions of covariates that include information on climate, hydrology, groundwater, and basin descriptors. Three classifiers to estimate flow states using covariates are tested on four contrasted regions in France: (a) a linear classifier with regularization (LASSO for least absolute shrinkage and selection operator) and two non‐linear non‐parametric classifiers, (b) a one‐hidden‐layer feedforward artificial neural network (ANN) classifier, and (c) a random forest (RF) classifier. The three classifiers are compared with a benchmark classifier (BC) that simply estimates dominant flow state for each month based on observations (without using covariates). The performance assessment over the period 2012–2016 carried out by cross‐validation shows that the three classifiers for flow state based on covariates outperformed the BC. This demonstrates the predictive power of the covariates. ANN is the classifier that globally achieves the best performance to predict the daily drying dynamics whereas both RF and LASSO tend to underestimate the proportion of drying states. The covariates are ranked in terms of relevance for each classifier. The monthly proportion of drying states provided by the discrete observation network has a major importance for the three classifiers ANN, LASSO, and RF. This may reflect the proclivity of a site to flow intermittence. ANN gives higher importance to climatic and hydrological covariates and its non‐linearity allows a greater degree of freedom.
Comparisons of the Performance of δ13C and δ18O of Fagus sylvatica, Pinus sylvestris, and Quercus petraea in the Record of Past Climate Variations

Climate reconstructions in temperate Europe have been widely based on oak species. However, other co‐occurring species, largely distributed in Europe, may be used for recording climate variability. In this paper, we documented the intertrees and interspecies variations over 1960–2007 of oxygen and carbon isotopic compositions in ring cellulose of Fagus sylvatica, Pinus sylvestris, and Quercus petraea co‐occurring in the Fontainebleau forest (France). Our results indicated that large levels of series replication (11 trees on average) were required to generate isotopic mean series representative of the populations. We calculated mean isotopic ratios higher in pine than in the deciduous species and hypothesized that these contrasts resulted from differences in stomatal conductance, phenology, and canopy structure and, for oxygen, also in water uptake depth and isotopic exchange rate. We found that δ18O and δ13C chronologies were significantly correlated to one another in the three species and responded primarily to air moisture and Tmax, which indicated that stomatal conductance was an important driver of changes in both types of records. We determined that the correlations were strong with the May to July climate variables in F. sylvatica and with the July and August ones in Q. petraea and P. sylvestris. We showed that the oxygen records were systematically more coherent than those of carbon. This study demonstrated that δ18O, and to a lesser extent δ13C, from the three different species are reliable proxies for reconstructing past hydroclimatic variations in Europe.
Aulacogen Formation in Response to Opening the Ailaoshan Ocean: Origin of the Qin-Fang Trough, South China

The Qin-Fang Trough, South China, trends northeast-southwest, orthogonal to the adjoining southern margin of the craton. The Devonian strata within the trough are unconformable on late Neoproterozoic units of the Yunkai Massif, indicating that strata within the trough are autochthonous. U-Pb ages and Hf isotope compositions of detrital zircons from the Silurian to Devonian succession are consistent with derivation from the massif. In comparisons of our data with those from equivalent units in the Ailaoshan Belt and Hainan Island, detrital zircons from the Silurian strata show similar age distributions and Hf isotope compositions, indicating that the three areas shared a common source and were adjacent to each other during the Silurian. In contrast, the age distributions of detrital zircons preserved in Devonian strata in the Qin-Fang area are different from those of equivalent units in the Ailaoshan Belt. This, along with the absence of Devonian strata on Hainan Island, suggests that the Qin-Fang area had separated from the Ailaoshan Belt by the Devonian. This change is linked to opening of the Ailaoshan Ocean, which was synchronous with expansion of the Qin-Fang Trough and the adjoining Youjiang Basin into epicontinental basins during the Devonian and Carboniferous. Combining these findings with temporal and spatial correlations, we conclude that the Qin-Fang Trough originated as an aulacogen: a “failed” rift of a three-armed rift system, with the other two rift arms evolving into the Ailaoshan Ocean during the opening of Paleo-Tethys. The Ailaoshan Ocean was an Atlantic-type oceanic basin with rifting commencing in the Early Silurian.
Sufentanil preserves hemodynamics and left ventricular function in patients with ischemic heart disease

Objective: Sufentanil has been reported to provide stable hemodynamics similar to other opioids. However, it has not been reliably established whether this stability can be attributed only to Sufentanil and translates into fully preserved left ventricular (LV) function. The purpose of this study was to evaluate the effect of Sufentanil on hemodynamics and LV systolic and diastolic function using invasive monitoring and echocardiography in patients with ischemic heart disease.
Methamphetamine-mediated endoplasmic reticulum (ER) stress induces type-1 programmed cell death in astrocytes via ATF6, IRE1α and PERK pathways

Methamphetamine (MA), a psychostimulant drug has been associated with a variety of neurotoxic effects which are thought to be mediated by induction of pro-inflammatory cytokines/chemokines, oxidative stress and damage to blood-brain-barrier. Conversely, the ER stress-mediated apoptosis has been implicated in several neurodegenerative diseases. However, its involvement in MA-mediated neurodegenerative effects remains largely unexplored. The present study was undertaken to assess the effect of MA on ER stress and its possible involvement in apoptosis. For this purpose, SVGA astrocytes were treated with MA, which induced the expressions of BiP and CHOP at both, mRNA and protein levels. This phenomenon was also confirmed in HFA and various regions of mouse brain. Assessment of IRE1α, ATF6 and PERK pathways further elucidated the mechanistic details underlying MA-mediated ER stress. Knockdown of various intermediate molecules in ER stress pathways using siRNA demonstrated reduction in MA-mediated CHOP. Finally, MA-mediated apoptosis was demonstrated via MTT assay and TUNEL staining. The involvement of ER stress in the apoptosis was demonstrated with the help of MTT and TUNEL assays in the presence of siRNA against various ER stress proteins. The apoptosis also involved activation of caspase-3 and caspase-9, which was reversed by knockdown with various siRNAs. Altogether, this is the first report demonstrating mechanistic details responsible for MA-mediated ER stress and its role in apoptosis. This study provides a novel group of targets that can be explored in future for management of MA-mediated cell death and MA-associated neurodegenerative disorders.
Formation of B-1 B Cells from Neonatal B-1 Transitional Cells Exhibits NF-κB Redundancy

The stages of development leading up to the formation of mature B-1 cells have not been identified. As a result, there is no basis for understanding why various genetic defects, and those in the classical or alternative NF-κB pathways in particular, differentially affect the B-1 and B-2 B cell lineages. In this article, we demonstrate that B-1 B cells are generated from transitional cell intermediates that emerge in a distinct neonatal wave of development that is sustained for ∼2 wk after birth and then declines as B-2 transitional cells predominate. We further show that, in contrast to the dependence of B-2 transitional cells on the alternative pathway, the survival of neonatal B-1 transitional cells and their maturation into B-1 B cells occurs as long as either alternative or classical NF-κB signaling is intact. On the basis of these results, we have generated a model of B-1 development that allows the defects in B-1 and B-2 cell production observed in various NF-κB–deficient strains of mice to be placed into a coherent cellular context.
Probabilistic Prediction and Forecast of Daily Suspended Sediment Concentration on the Upper Yangtze River

Sediment transport in suspension can represent more than 90% of a river's total annual flux of sediment. In the case of the Yangtze River, more than 99% of the sediment supplied to the sea is suspended load. Suspended sediment is thus an important component of the total sediment load, with implications for channel dynamics, landscape evolution, ecology, and human‐related activities. For hydrological management of large basins such as the Yangtze River, knowledge of the processes governing suspended sediment concentration (SSC) is essential. An analysis of the temporal variation of SSC for the Upper Yangtze basin (defined at Pingshan station) is presented here. For this purpose, a database of 50 years of concurrent discharge and SSC measurements, made by the Yangtze River Commission, is used. The analysis is made using a novel probabilistic data‐driven technique, the Generalized Pareto Uncertainty (GPU). This technique allows for the testing of several strategies of prediction and forecast applied to a time series of SSC and streamflow. Changing between local or seasonal variables to feed these strategies, we inferred that although the main driver of the SSC transport is flow (as reported by previous authors), sediment storage is also a major control. Furthermore, the maximum necessary time lag for forecasts made with the data is on the order of one week, which provides one indication of the time scale of the local processes of SSC transport in the Upper Yangtze. In this paper, limitations and data requirements of the GPU methodology are also discussed.
Real-time head pose estimation for driver assistance system using low-cost on-board computer

We propose a fast head pose estimation method using monocular video. It is highly optimized for on-board computers and for driving situations, which is applicable to existing low-cost on-board computer for cars and suitable for high real-time driver assistance systems. In our algorithm pipeline, the face detection step eliminates slow floating point computations using pixel intensity binary test, and reduce search scope effectively. In the face alignment step, we utilize the high performance of local binary feature and extend the single pose regression model to handle large rotations. The pose estimation step uses a mean rigid face model to calculate head pose fast by solving 2D-3D correspondence. To reduce computation further, we bypass or simplify pipeline steps using previous frame result, and redo the full pipeline adaptively. Experiments show our method is more efficient than existing approaches, which makes high real-time applications for on-board computers possible.
The Measurement of Cognitive Complexity and Its Relationship With Political Extremism

Three studies tested the relationship between political extremism and cognitive complexity in an adult sample (N = 135), a sample of students (N = 145), and a sample of political party members (N = 47). According to value pluralism theory, advocates of extreme ideologies exhibit low levels of cognitive complexity. Context theory, in contrast, states that extremists think in a more complex and sophisticated way about politics. In accordance with context theory, significant positive correlations between cognitive complexity and extremist ideology were found in all samples. The results of these studies also revealed weak correlations among the cognitive complexity instruments used in previous research. Problems concerning the measurement of cognitive style and cognitive complexity are discussed.