Miracle-dz/UniFAR-FTUs huggingface dataset:
Hybrid Deep Learning-Gaussian Process Network for Pedestrian Lane Detection in Unstructured Scenes

Pedestrian lane detection is an important task in many assistive and autonomous navigation systems. This article presents a new approach for pedestrian lane detection in unstructured environments, where the pedestrian lanes can have arbitrary surfaces with no painted markers. In this approach, a hybrid deep learning-Gaussian process (DL-GP) network is proposed to segment a scene image into lane and background regions. The network combines a compact convolutional encoder–decoder net and a powerful nonparametric hierarchical GP classifier. The resulting network with a smaller number of trainable parameters helps mitigate the overfitting problem while maintaining the modeling power. In addition to the segmentation output for each test image, the network also generates a map of uncertainty—a measure that is negatively correlated with the confidence level with which we can trust the segmentation. This measure is important for pedestrian lane-detection applications, since its prediction affects the safety of its users. We also introduce a new data set of 5000 images for training and evaluating the pedestrian lane-detection algorithms. This data set is expected to facilitate research in pedestrian lane detection, especially the application of DL in this area. Evaluated on this data set, the proposed network shows significant performance improvements compared with several existing methods.
Quantitative Flow Cytometric Evaluation of Oxidative Stress and Mitochondrial Impairment in RAW 264.7 Macrophages after Exposure to Pristine, Acid Functionalized, or Annealed Carbon Nanotubes

Conventional nanotoxicological assays are subjected to various interferences with nanoparticles and especially carbon nanotubes. A multiparametric flow cytometry (FCM) methodology was developed here as an alternative to quantify oxidative stress, mitochondrial impairment, and later cytotoxic and genotoxic events. The experiments were conducted on RAW264.7 macrophages, exposed for 90 min or 24 h-exposure with three types of multiwalled carbon nanotubes (MWCNTs): pristine (Nanocyl™ CNT), acid functionalized (CNTf), or annealed treatment (CNTa). An original combination of reactive oxygen species (ROS) probes allowed the simultaneous quantifications of broad-spectrum ROS, superoxide anion (O2•−), and hydroxyl radical (•OH). All MWCNTs types induced a slight increase of broad ROS levels regardless of earlier antioxidant catalase activity. CNTf strongly stimulated the O2•− production. The •OH production was downregulated for all MWCNTs due to their scavenging capacity. The latter was quantified in a cell-free system by electron paramagnetic resonance spectroscopy (EPR). Further FCM-based assessment revealed early biological damages with a mitochondrial membrane potential collapse, followed by late cytotoxicity with chromatin decondensation. The combined evaluation by FCM analysis and cell-free techniques led to a better understanding of the impacts of MWCNTs surface treatments on the oxidative stress and related biological response.
Functional proteomics interrogation of the kinome identifies MRCKA as a therapeutic target in high-grade serous ovarian carcinoma

Kinome profiling of ovarian tumors reveals a way to treat patients and get a step ahead of drug resistance. Out of the dark, a new kinase target in ovarian cancer Ovarian cancer is frequently fatal; it is difficult to detect and challenging to treat. Uncovering genetic signatures has done little to improve clinical outcomes. Using cell lines and patient tumors, Kurimchak et al. analyzed the functional kinome of high-grade serous ovarian carcinoma (HGSOC) and identified a relatively uncharacterized kinase called MRCKA, among potentially others, as being important for HGSOC cell survival and tumor growth. Decreasing MRCKA abundance or pharmacologically inhibiting its kinase activity killed HGSOC cells but, as with so many growth inhibitors, led to activation of other survival-promoting kinases in remaining cells. Cotargeting one of these (PAK1) or cotreating cells with platinum-based chemotherapy had greater cytotoxicity. The findings identify multiple potential therapeutic strategies to treat HGSOC and prevent drug resistance in patients. High-grade serous ovarian carcinoma (HGSOC) is the most lethal gynecological cancer with few effective, targeted therapies. HGSOC tumors exhibit genomic instability with frequent alterations in the protein kinome; however, only a small fraction of the kinome has been therapeutically targeted in HGSOC. Using multiplexed inhibitor beads and mass spectrometry, we mapped the kinome landscape of HGSOC tumors from patients and patient-derived xenograft models. The data revealed a prevalent signature consisting of established HGSOC driver kinases, as well as several kinases previously unexplored in HGSOC. Loss-of-function analysis of these kinases in HGSOC cells indicated MRCKA (also known as CDC42BPA) as a putative therapeutic target. Characterization of the effects of MRCKA knockdown in established HGSOC cell lines demonstrated that MRCKA was integral to signaling that regulated the cell cycle checkpoint, focal adhesion, and actin remodeling, as well as cell migration, proliferation, and survival. Moreover, inhibition of MRCKA using the small-molecule BDP9066 decreased cell proliferation and spheroid formation and induced apoptosis in HGSOC cells, suggesting that MRCKA may be a promising therapeutic target for the treatment of HGSOC.
Temperature-Modulated Micromechanical Thermal Analysis with Microstring Resonators Detects Multiple Coherent Features of Small Molecule Glass Transition

Micromechanical Thermal Analysis utilizes microstring resonators to analyze a minimum amount of sample to obtain both the thermal and mechanical responses of the sample during a heating ramp. We introduce a modulated setup by superimposing a sinusoidal heating on the linear heating and implementing a post-measurement data deconvolution process. This setup is utilized to take a closer look at the glass transition as an important fundamental feature of amorphous matter with relations to the processing and physical stability of small molecule drugs. With an additionally developed image and qualitative mode shape analysis, we are able to separate distinct features of the glass transition process and explain a previously observed two-fold change in resonance frequency. The results from this setup indicate the detection of initial relaxation to viscous flow onset as well as differences in mode responsivity and possible changes in the primary resonance mode of the string resonators. The modulated setup is helpful to distinguish these processes during the glass transition with varying responses in the frequency and quality factor domain and offers a more robust way to detect the glass transition compared to previously developed methods. Furthermore, practical and theoretical considerations are discussed when performing measurements on string resonators (and comparable emerging analytical techniques) for physicochemical characterization.
Foxn4 is a temporal identity factor conferring mid/late-early retinal competence and involved in retinal synaptogenesis

Significance Organogenesis, an evolutionarily refined process which is so complicated, delicate, yet replicable, is all about time and space. Only until recently have scientists realized that the temporal identity of Drosophila neuroblasts is controlled by cascades of temporal transcription factors (tTFs), but the temporal regulation mechanism is poorly understood in vertebrates. We show that Foxn4 functions as a tTF to confer mammalian retinal progenitors (RPCs) with the competence to generate mid/late-early cell types while suppressing the immediate-early cell type. Our data thus identify a missing member of the tTF cascade that controls RPC temporal identities to ensure the generation of proper retinal neuronal diversity, and provide an important insight for understanding how cell-fate transitions are guided during vertebrate organogenesis. During development, neural progenitors change their competence states over time to sequentially generate different types of neurons and glia. Several cascades of temporal transcription factors (tTFs) have been discovered in Drosophila to control the temporal identity of neuroblasts, but the temporal regulation mechanism is poorly understood in vertebrates. Mammalian retinal progenitor cells (RPCs) give rise to several types of neuronal and glial cells following a sequential yet overlapping temporal order. Here, by temporal cluster analysis, RNA-sequencing analysis, and loss-of-function and gain-of-function studies, we show that the Fox domain TF Foxn4 functions as a tTF during retinogenesis to confer RPCs with the competence to generate the mid/late-early cell types: amacrine, horizontal, cone, and rod cells, while suppressing the competence of generating the immediate-early cell type: retinal ganglion cells (RGCs). In early embryonic retinas, Foxn4 inactivation causes down-regulation of photoreceptor marker genes and decreased photoreceptor generation but increased RGC production, whereas its overexpression has the opposite effect. Just as in Drosophila, Foxn4 appears to positively regulate its downstream tTF Casz1 while negatively regulating its upstream tTF Ikzf1. Moreover, retina-specific ablation of Foxn4 reveals that it may be indirectly involved in the synaptogenesis, establishment of laminar structure, visual signal transmission, and long-term maintenance of the retina. Together, our data provide evidence that Foxn4 acts as a tTF to bias RPCs toward the mid/late-early cell fates and identify a missing member of the tTF cascade that controls RPC temporal identities to ensure the generation of proper neuronal diversity in the retina.
Inorganic fluoride and functions of brain

Abstract Although actively disputed and questioned, it has been proposed that chronic exposure to inorganic fluoride (F−) is toxic for brain. The major question for this review was whether an excessive F− intake is causally related to adverse neurological and cognitive health conditions in human beings and animals. The paper systematically and critically summarizes the findings of the studies showing positive associations between F− intoxication and various intellectual defects, as well as of those which attempted to clarify the nature of F− neurotoxicity. Many works provide support for a link between pre- and postnatal F− exposure and structural and functional changes in the central nervous system responsible for neurological and cognitive disorders. The mechanisms suggested to underlie F− neurotoxicity include the disturbances in synaptic transmission and synaptic plasticity, premature death of neurons, altered activities of components of intracellular signaling cascades, impaired protein synthesis, deficit of neurotrophic and transcriptional factors, oxidative stress, metabolic changes, inflammatory processes. However, the majority of works have been performed on laboratory rodents using such F− doses which are never exist in the nature even in the regions of endemic fluorosis. Thus, this kind of treatment is hardly comparable with human exposure even taking into account the higher rate of F− clearance in animals. Of special importance are the data collected on humans chronically consuming excessive F− doses in the regions of endemic fluorosis or contacting with toxic F− compounds at industrial sites, but those works are scarce and often criticized due to low quality. New, expertly performed studies with repeated exposure assessment in independent populations are needed to prove an ability of F− to impair neurological and intellectual development of human beings and to understand the molecular mechanisms implicated in F−-induced neurotoxicity.
ABCA12 regulates insulin secretion from β‐cells

Dysregulation of lipid homeostasis is intimately associated with defects in insulin secretion, a key feature of type 2 diabetes. Here, we explore the role of the putative lipid transporter ABCA12 in regulating insulin secretion from β‐cells. Mice with β‐cell‐specific deletion of Abca12 display impaired glucose‐stimulated insulin secretion and eventual islet inflammation and β‐cell death. ABCA12's action in the pancreas is independent of changes in the abundance of two other cholesterol transporters, ABCA1 and ABCG1, or of changes in cellular cholesterol or ceramide content. Instead, loss of ABCA12 results in defects in the genesis and fusion of insulin secretory granules and increases in the abundance of lipid rafts at the cell membrane. These changes are associated with dysregulation of the small GTPase CDC42 and with decreased actin polymerisation. Our findings establish a new, pleiotropic role for ABCA12 in regulating pancreatic lipid homeostasis and insulin secretion.
Characteristics, dynamic changes, and prognostic significance of TCR repertoire profiling in patients with renal cell carcinoma

The co‐evolving tumour cells and the systemic immune environment are mutually dysregulated. Tumours affect the immune response in a complex manner. For example, although lymphocytes are mobilized in response to tumours, their function is impaired by tumour progression. This study aimed to explore how the baseline and dynamic renal cell carcinoma (RCC) tumour burdens affect the T‐cell repertoire, and whether the baseline T‐cell receptor β‐chain (TCRB) diversity predicts prognosis. To characterise the TCRB repertoire, the baseline and follow‐up peripheral TCRB repertoires of 45 patients with RCC and 2 patients with benign renal disease patients were examined using high‐throughput TCRB sequencing. To explain the significance of TCRB diversity, 56 peripheral leukocyte samples from 28 patients before and after surgery were subjected to transcriptome sequencing. To validate the results, an advanced RCC patient's sample was subjected to single‐cell RNA sequencing (scRNA, 10x Genomics). Higher TCRB diversity was found to be correlated with a higher lymphocyte‐to‐neutrophil ratio, especially indicating more naïve T cells. High‐baseline TCRB diversity predicted a better prognosis for stage IV patients, and different tumour burdens exerted distinct effects on the immune status. The pre‐operative TCRB diversity was significantly higher in benign and stage I (low tumour burden) RCC patients than in stage IV (high tumour burden) patients. After the tumour burden of advanced patients was mostly relieved, we observed that the TCRB diversity was restored, T‐cell exhaustion was reduced, and naïve T‐cells were mobilized. It was demonstrated that the circulating TCRB repertoire could reflect the immune status and predict prognosis, and to some extent that cytoreductive nephrectomy (CN) reduces the burden of the immune system in advanced patients, which might provide a good opportunity for immunotherapy. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Patterned perturbation of inhibition can reveal the dynamical structure of neural processing

Perturbation of neuronal activity is key to understanding the brain’s functional properties, however, intervention studies typically perturb neurons in a nonspecific manner. Recent optogenetics techniques have enabled patterned perturbations, in which specific patterns of activity can be invoked in identified target neurons to reveal more specific cortical function. Here, we argue that patterned perturbation of neurons is in fact necessary to reveal the specific dynamics of inhibitory stabilization, emerging in cortical networks with strong excitatory and inhibitory functional subnetworks, as recently reported in mouse visual cortex. We propose a specific perturbative signature of these networks and investigate how this can be measured under different experimental conditions. Functionally, rapid spontaneous transitions between selective ensembles of neurons emerge in such networks, consistent with experimental results. Our study outlines the dynamical and functional properties of feature-specific inhibitory-stabilized networks, and suggests experimental protocols that can be used to detect them in the intact cortex.
A New Edible Film to Produce In Vitro Meat

In vitro meat is a novel concept of food science and biotechnology. Methods to produce in vitro meat employ muscle cells cultivated on a scaffold in a serum-free medium using a bioreactor. The microstructure of the scaffold is a key factor, because muscle cells must be oriented to generate parallel alignments of fibers. This work aimed to develop a new scaffold (microstructured film) to grow muscle fibers. The microstructured edible films were made using micromolding technology. A micromold was tailor-made using a laser cutting machine to obtain parallel fibers with a diameter in the range of 70–90 µm. Edible films were made by means of solvent casting using non-mammalian biopolymers. Myoblasts were cultured on flat and microstructured films at three cell densities. Cells on the microstructured films grew with a muscle fiber morphology, but in the case of using the flat film, they only produced unorganized cell proliferation. Myogenic markers were assessed using quantitative polymerase chain reaction. After 14 days, the expression of desmin, myogenin, and myosin heavy chain were significantly higher in microstructured films compared to the flat films. The formation of fiber morphology and the high expression of myogenic markers indicated that a microstructured edible film can be used for the production of in vitro meat.
PCR-Restriction Fragment Length Polymorphism and Pulsed-Field Gel Electrophoresis Characterization of Listeria monocytogenes Isolates from Ready-to-Eat Foods, the Food Processing Environment, and Clinical Samples in South Africa.

ABSTRACT Listeria monocytogenes is a ubiquitous, intracellular foodborne pathogen that is responsible for invasive listeriosis. The ability of L. monocytogenes to cause disease has some correlation with the serotypes of a specific lineage group, making the identification of lineage groups important for epidemiological analysis. The development of typing methods to link the strains of L. monocytogenes to an outbreak of listeriosis would help minimize the spread of the disease. The aim of this study was to design a PCR-restriction fragment length polymorphism (RFLP) method to differentiate between the lineage groups of L. monocytogenes. PCR-amplified fragments of the hly gene for 12 serotypes of L. monocytogenes were sequenced, aligned, and analyzed with the BioEdit program, and single nucleotide polymorphisms (SNPs) within regions of this gene were identified. Because of the difficulty in acquiring a serotype 4ab reference strain, this serotype was not included in this study. We tested the specificity and accuracy of the PCR-RFLP method on these L. monocytogenes reference strains and validated the method with 172 L. monocytogenes strains recovered from humans, food, and the food processing environment in 2000 to 2002 and 2008 to 2010 from regions within South Africa. PCR-RFLP analysis applied in this study placed L. monocytogenes serotypes into one of three lineage groups based on the sequence differences and SNPs within each lineage group. The SNPs were conserved in a region where RFLP analysis could be applied for a distinction between L. monocytogenes lineage groups. HIGHLIGHTS
Timing and magnitude of Southern Ocean sea ice/carbon cycle feedbacks

Significance Atmospheric carbon was sequestered in the ocean during glacial periods, but the processes responsible are not understood. Southern Ocean (SO) sea ice has been proposed as a link between several processes of carbon sequestration. This study analyzes the effect of SO sea ice on ocean ventilation in a 784,000-y climate model simulation. The results show that SO sea ice can dramatically reduce ocean ventilation by reducing the atmospheric exposure time of surface waters and by decreasing the vertical mixing of deep ocean waters. Sensitivity tests of the two mechanisms with a carbon cycle model show a 40-ppm reduction of atmospheric CO2, half the glacial/interglacial difference, with ocean stratification playing the leading role in both magnitude and timing. The Southern Ocean (SO) played a prominent role in the exchange of carbon between ocean and atmosphere on glacial timescales through its regulation of deep ocean ventilation. Previous studies indicated that SO sea ice could dynamically link several processes of carbon sequestration, but these studies relied on models with simplified ocean and sea ice dynamics or snapshot simulations with general circulation models. Here, we use a transient run of an intermediate complexity climate model, covering the past eight glacial cycles, to investigate the orbital-scale dynamics of deep ocean ventilation changes due to SO sea ice. Cold climates increase sea ice cover, sea ice export, and Antarctic Bottom Water formation, which are accompanied by increased SO upwelling, stronger poleward export of Circumpolar Deep Water, and a reduction of the atmospheric exposure time of surface waters by a factor of 10. Moreover, increased brine formation around Antarctica enhances deep ocean stratification, which could act to decrease vertical mixing by a factor of four compared with the current climate. Sensitivity tests with a steady-state carbon cycle model indicate that the two mechanisms combined can reduce atmospheric carbon by 40 ppm, with ocean stratification acting early within a glacial cycle to amplify the carbon cycle response.
Prognostic value of SUVmax on 18F-fluorodeoxyglucose PET/CT scan in patients with malignant pleural mesothelioma

Introduction The maximum standardized uptake value (SUVmax) in 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) may be of prognostic significance for patients with malignant pleural mesothelioma (MPM). This retrospective study aimed to investigate the prognostic value of the SUVmax in patients with MPM. Materials and methods Medical records were retrospectively reviewed for the patients who were diagnosed with histopathologically proven MPM between 2009 and 2018 at Samsung Medical Center. For each patient, SUVmax was calculated for the primary lesion on PET/CT. To determine optimal cutoff values for predicting mortality, receiver operating characteristic curves were used. Results Among the 54 study patients, 34 (63.0%) had epithelioid subtype, 13 (24.1%) had sarcomatoid or biphasic subtype, and 7 (13.0%) had mesothelioma, not otherwise specified (NOS). The median overall survival (OS) was 8.7 months, and the median SUVmax was 9.9. The median values of SUVmax were 5.5 in patients with epithelioid subtype, 11.7 in those with sarcomatoid/biphasic subtype, and 13.3 in those with NOS subtype (P = 0.003). The optimal cutoff values of SUVmax to predict mortality were 10.1 in all patients, and 8.5 in patients with epithelioid subtype. In multivariate analysis, SUVmax was significantly associated with overall survival in all patients (P = 0.003) and in patients with epithelioid subtype (P = 0.012), but not in those with non-epithelioid subtype. Conclusions SUVmax in PET/CT is an independent prognostic factor in patients with MPM, especially those with epithelioid subtype. The histologic subtype of MPM should be considered when evaluating the prognostic significance of SUVmax.