Miracle-dz/UniFAR-FTUs huggingface dataset:
Fibroblast Growth Factor-1 Activates Neurons in the Arcuate Nucleus and Dorsal Vagal Complex

Central administration of fibroblast growth factor-1 (FGF1) results in long-lasting resolution of hyperglycemia in various rodent models, but the pre- and postsynaptic mechanisms mediating the central effects of FGF1 are unknown. Here we utilize electrophysiology recordings from neuronal populations in the arcuate nucleus of the hypothalamus (ARH), nucleus of the solitary tract (NTS), and area postrema (AP) to investigate the mechanisms underlying FGF1 actions. While FGF1 did not alter membrane potential in ARH-NPY-GFP neurons, it reversibly depolarized 83% of ARH-POMC-EGFP neurons and decreased the frequency of inhibitory inputs onto ARH-POMC-EGFP neurons. This depolarizing effect persisted in the presence of FGF receptor (R) blocker FIIN1, but was blocked by pretreatment with the voltage-gated sodium channel (VGSC) blocker tetrodotoxin (TTX). Non-FGF1 subfamilies can activate vascular endothelial growth factor receptors (VEGFR). Surprisingly, the VEGFR inhibitors axitinib and BMS605541 blocked FGF1 effects on ARH-POMC-EGFP neurons. We also demonstrate that FGF1 induces c-Fos in the dorsal vagal complex, activates NTS-NPY-GFP neurons through a FGFR mediated pathway, and requires VGSCs to activate AP neurons. We conclude that FGF1 acts in multiple brain regions independent of FGFRs. These studies present anatomical and mechanistic pathways for the future investigation of the pharmacological and physiological role of FGF1 in metabolic processes.
Soil Bacterial Community in the Multiple Cropping System Increased Grain Yield Within 40 Cultivation Years

The shortage of land resources restricts the sustainable development of agricultural production. Multiple cropping has been widely used in Southern China, but whether the continuous planting will cause a decline in soil quality and crop yield is unclear. To test whether multiple cropping could increase grain yield, we investigated the farmlands with different cultivation years (10–20 years, 20–40 years, and >40 years). Results showed that tobacco-rice multiple cropping rotation significantly increased soil pH, nitrogen nutrient content, and grain yield, and it increased the richness of the bacterial community. The farmland with 20–40 years of cultivation has the highest soil organic carbon (SOC), ammonium nitrogen, and grain yield, but there is no significant difference in the diversity and structure of the bacterial community in farmlands with different cultivation years. The molecular ecological network indicated that the stability of the bacterial community decreased across the cultivation years, which may result in a decline of farmland yields in multiple cropping system> 40 years. The Acidobacteria members as the keystone taxa (Zi ≥ 2.5 or Pi ≥ 0.62) appeared in the tobacco-rice multiple cropping rotation farmlands, and the highest abundance of Acidobacteria was found in the farmland with the highest SOC and ammonium nitrogen content, suggesting Acidobacteria Gp4, GP7, GP12, and GP17 are important taxa involved in the soil carbon and nitrogen cycle. Therefore, in this study, the multiple cropping systems for 20 years will not reduce the crop production potential, but they cannot last for more than 40 years. This study provides insights for ensuring soil quality and enhancing sustainable agricultural production capacity.
Mapping Detroit: land, community and shaping a city

Berghauser Pont, M. , P. Haupt. 2010. Spacematrix. Space, Density and Urban Form. Rotterdam: NAi Publishers. Durand, J. N. L. 1801. Receuil et parallèle des édifices de tout genre, ancients et modernes [selection and parallel comparison of buildings of all kinds, ancient and modern]. Paris: École Polytechnique. Durand, J. N. L. 1819. Partie graphique des cours d’ architecture [Précis of the lectures on architecture: with graphic portion of the lectures on architecture]. Paris: École PolytechniqueParis. Ferriss, H. 1929. The Metropolis of Tomorrow. Reprinted 2005. New York: Dover. March, L. , and P. steadman. 1971. The Geometry of Environment: An Introduction to Spatial Organization in Design. London: RiBA Publications. Martin, L. , and L. March. 1972. Urban Space and Structures. Cambridge: Cambridge University Press. shayesteh H and J. P. steadman. 2015. “Coevolution of Urban Form and Built Form: A New Typomorphological Model for Tehran. ” in Environment and Planning B: Planning & Design. doi:10.1068/b140002p steadman, P. 1979. The Evolution of Designs. Biological Analogy in Architecture and the Applied Arts. Cambridge: Cambridge University Press. steadman, P. 1983. Architectural Morphology. London: Pion Press. steadman, J. P. 1994. “Built Forms and Building Types: some speculations. ” Environment and Planning B: Planning & Design 21: s7–s30. steadman J. P. 2001. “Binary encoding of a Class of Rectangular Built Forms. ” in Space Syntax Third International Symposium, edited by J. Peponis, J. wineman, and s. Bafna, 9.1–9.16. Ann Arbor: Taubman College of Architecture and Urban Planning. steadman, J. P., and L. J. Mitchell. 2010. “Architectural Morphospace: Mapping worlds of Built Forms. ” Environment and Planning B: Planning & Design 37: 197–220.
Curved open-channel flows. A numerical study

The flow of water through a river bend can be characterized as a turbulent open-channel flow that is dominated by streamline curvature. In order to adequately manage the planimetry of meandering rivers and the according safety aspects, the features of the flow and the associated turbulence have to be understood well. This thesis presents results of detailed numerical simulations of curved open-channel flows on a laboratory scale. These flows can basically be considered as downscaled river bend flows. The presented results provide a broad image of the behavior of curved open-channel flows in general and their characteristics with respect to the secondary flow, the bed shear stresses and turbulence in particular. Hereby, these results also facilitate further development of parameterizations of these key bend flow features for lower-dimensional modeling tools that are used in the engineering practice.
Dysregulation of Intestinal Physiology by Aflatoxicosis in the Gilthead Seabream (Sparus aurata)

Aflatoxin B1 (AFB1) is a mycotoxin often present in food. This study aimed to understand the physiological effects of AFB1 on the seabream (Sparus aurata) gastrointestinal system. In a first in vitro approach, we investigated ion transport using the short-circuit current (Isc) technique in Ussing chambers in the anterior intestine (AI). Application of apical/luminal AFB1 concentrations of 8 and 16 μM to healthy tissues was without effect on tissue transepithelial electrical resistance (TER), and apparent tissue permeability (Papp) was measured using fluorescein FITC (4 kD). However, it resulted in dose-related effects on Isc. In a second approach, seabream juveniles fed with different AFB1 concentrations (1 and 2 mg AFB1 kg−1 fish feed) for 85 days showed significantly reduced gill Na+/K+-ATPase (NKA) and H+-ATPase (HA) activities in the posterior intestine (PI). Moreover, dietary AFB1 modified Isc in the AI and PI, significantly affecting TER in the AI. To understand this effect on TER, we analyzed the expression of nine claudins and three occludins as markers of intestinal architecture and permeability using qPCR. Around 80% of the genes presented significantly different relative mRNA expression between AI and PI and had concomitant sensitivity to dietary AFB1. Based on the results of our in vitro, in vivo, and molecular approaches, we conclude that the effects of dietary AFB1 in the gastrointestinal system are at the base of the previously reported growth impairment caused by AFB1 in fish.
Tracing Human IgE B Cell Antigen Receptor-Bearing Cells With a Monoclonal Anti-Human IgE Antibody That Specifically Recognizes Non-Receptor-Bound IgE

Up to 30% of the population suffers from immunoglobulin E (IgE)-mediated allergies. Despite current stepwise gating approaches, the unambiguous identification of human IgE-producing cells by flow cytometry and immunohistology remains challenging. This is mainly due to the scarcity of these cells and the fact that IgE is not only expressed in a membrane-bound form on the surface of IgE-producing cells in form of the B cell antigen receptor (BCR), but is more frequently found on various cell types bound to the low and high affinity receptors, CD23 and FcϵRI, respectively. Here we sought to develop a sequential gating strategy for unambiguous detection of cells bearing the IgE BCR on their surface. To that aim we first tested the monoclonal anti-IgE antibody omalizumab for its ability to discriminate between IgE BCR and receptor-bound IgE using cells producing IgE or bearing IgE bound to CD23 as well as basophils exhibiting FcϵRI receptor-bound IgE. Using flow cytometry, we demonstrated that omalizumab recognized IgE producing cells with a high sensitivity of up to 1 IgE+ cell in 1000 human peripheral blood mononuclear cells (PBMCs). These results were confirmed by confocal microscopy both in cell suspensions as well as in nasal polyp tissue sections. Finally, we established a consecutive gating strategy allowing the clear identification of class-switched, allergen-specific IgE+ memory B cells and plasmablasts/plasma cells in human PBMCs. Birch pollen specific IgE+ memory B cells represented on average 0.734% of total CD19+ B cells in allergic patients after allergen exposure. Thus, we developed a new protocol for exclusive staining of non-receptor bound allergen-specific IgE+ B cell subsets in human samples.
Undetectable Production of the VIM-1 Carbapenemase in an Atlantibacter hermannii Clinical Isolate

The differential expression of VIM-1 in Atlantibacter hermannii WEB-2 and Enterobacter hormaechei ssp. hoffmannii WEB-1 clinical isolates from a rectal swab of a hospitalized patient in France was investigated. A. hermannii WEB-2 was resistant to all β-lactams except carbapenems. It produced ESBL SHV-12, but the Carba NP test failed to detect any carbapenemase activity despite the production of VIM-1. Conversely, E. hormaechei WEB-1, previously recovered from the same patient, was positive for the detection of carbapenemase activity. The blaVIM–1 gene was located on a plasmid and embedded within class 1 integron. Both plasmids were of the same IncA incompatibility group and conferred the same resistance pattern when electroporated in Escherichia coli TOP10 or Enterobacter cloacae CIP7933. Quantitative RT-PCR experiments indicated a weaker replication of pWEB-2 in A. hermannii as compared to E. hormaechei. An isogenic mutant of A. hermannii WEB-2 selected after sequential passages with increased concentrations of imipenem possessed higher MICs for carbapenems and cephalosporins including cefiderocol, higher levels of the blaVIM–1 gene transcripts, and detectable carbapenemase activity using the Carba NP test. Assessment of read coverage demonstrated that a duplication of the region surrounding blaVIM–1 gene occurred in the A. hermannii mutant with detectable carbapenemase activity. The lack of detection of the VIM-1 carbapenemase activity in A. hermannii WEB-2 isolate was likely due to a weak replication of the IncA plasmid harboring the blaVIM–1 gene. Imipenem as selective pressure led to a duplication of this gene on the plasmid and to the restoration of a significant carbapenem-hydrolyzing phenotype.
Whole Genome Sequencing of Staphylococci Isolated From Bovine Milk Samples

Staphylococci are among the commonly isolated bacteria from intramammary infections in bovines, where Staphylococcus aureus is the most studied species. This species carries a variety of virulence genes, contributing to bacterial survival and spread. Less is known about non-aureus staphylococci (NAS) and their range of virulence genes and mechanisms, but they are the most frequently isolated bacteria from bovine milk. Staphylococci can also carry a range of antimicrobial resistance genes, complicating treatment of the infections they cause. We used Illumina sequencing to whole genome sequence 93 staphylococcal isolates selected from a collection of staphylococcal isolates; 45 S. aureus isolates and 48 NAS isolates from 16 different species, determining their content of antimicrobial resistance genes and virulence genes. Antimicrobial resistance genes were frequently observed in the NAS species as a group compared to S. aureus. However, the lincosamide resistance gene lnuA and penicillin resistance gene blaZ were frequently identified in NAS, as well as a small number of S. aureus. The erm genes conferring macrolide resistance were also identified in several NAS isolates and in a small number of S. aureus isolates. In most S. aureus isolates, no antimicrobial resistance genes were detected, but in five S. aureus isolates three to six resistance genes were identified and all five of these carried the mecA gene. Virulence genes were more frequently identified in S. aureus, which contained on average five times more virulence genes compared to NAS. Among the NAS species there were also differences in content of virulence genes, such as S. chromogenes with a higher average number of virulence genes. By determining the content of a large selection of virulence genes and antimicrobial resistance genes in S. aureus and 16 different NAS species our results contribute with knowledge regarding the genetic basis for virulence and antimicrobial resistance in bovine staphylococci, especially the less studied NAS. The results can create a broader basis for further research into the virulence mechanisms of this important group of bacteria in bovine intramammary infections.
Enzymatic Switching Between Archaeal DNA Polymerases Facilitates Abasic Site Bypass

Abasic sites are among the most abundant DNA lesions encountered by cells. Their replication requires actions of specialized DNA polymerases. Herein, two archaeal specialized DNA polymerases were examined for their capability to perform translesion DNA synthesis (TLS) on the lesion, including Sulfolobuss islandicus Dpo2 of B-family, and Dpo4 of Y-family. We found neither Dpo2 nor Dpo4 is efficient to complete abasic sites bypass alone, but their sequential actions promote lesion bypass. Enzyme kinetics studies further revealed that the Dpo4’s activity is significantly inhibited at +1 to +3 site past the lesion, at which Dpo2 efficiently extends the primer termini. Furthermore, their activities are inhibited upon synthesis of 5–6 nt TLS patches. Once handed over to Dpo1, these substrates basically inactivate its exonuclease, enabling the transition from proofreading to polymerization of the replicase. Collectively, by functioning as an “extender” to catalyze further DNA synthesis past the lesion, Dpo2 bridges the activity gap between Dpo4 and Dpo1 in the archaeal TLS process, thus achieving more efficient lesion bypass.
Theta Oscillations at Subthalamic Region Predicts Hypomania State After Deep Brain Stimulation in Parkinson's Disease

Subthalamic nucleus (STN) deep brain stimulation (DBS) is an effective treatment for the motor impairments of patients with advanced Parkinson's disease. However, mood or behavioral changes, such as mania, hypomania, and impulsive disorders, can occur postoperatively. It has been suggested that these symptoms are associated with the stimulation of the limbic subregion of the STN. Electrophysiological studies demonstrate that the low-frequency activities in ventral STN are modulated during emotional processing. In this study, we report 22 patients with Parkinson's disease who underwent STN DBS for treatment of motor impairment and presented stimulation-induced mood elevation during initial postoperative programming. The contact at which a euphoric state was elicited by stimulation was termed as the hypomania-inducing contact (HIC) and was further correlated with intraoperative local field potential recorded during the descending of DBS electrodes. The power of four frequency bands, namely, θ (4–7 Hz), α (7–10 Hz), β (13–35 Hz), and γ (40–60 Hz), were determined by a non-linear variation of the spectrogram using the concentration of frequency of time (conceFT). The depth of maximum θ power is located approximately 2 mm below HIC on average and has significant correlation with the location of contacts (r = 0.676, p < 0.001), even after partializing the effect of α and β, respectively (r = 0.474, p = 0.022; r = 0.461, p = 0.027). The occurrence of HIC was not associated with patient-specific characteristics such as age, gender, disease duration, motor or non-motor symptoms before the operation, or improvement after stimulation. Taken together, these data suggest that the location of maximum θ power is associated with the stimulation-induced hypomania and the prediction of θ power is frequency specific. Our results provide further information to refine targeting intraoperatively and select stimulation contacts in programming.
An Artificial Intelligence Cyberattack Detection System to Improve Threat Reaction in e-Health

In the e-Health domain, new and continuously evolving threats emerge every day. The security of e-Health telemonitoring systems is no longer negligible. In this paper, we propose a Cyberattack Detection System (CADS) model that exploits artificial intelligence techniques to detect anomalies without requiring a security analyst, explain the malicious activity, and display suspected attack data to health-care personnel for feedback. The system description is contextualized to the case of the hacked remote patient health telemonitoring.
Research on Boundary Layer Effect in Fractured Reservoirs Based on Pore-Scale Models

It is of great significance to study the seepage characteristics of heavy oil reservoirs, which are conducive to the efficient development of resources. Boundary layer effect (BLE) exists in the pore-scale flow process of macromolecular fluid media, which is different from the flow law of conventional fluid in the pore, yet the influence of BLE is ignored in the previous pore-scale simulation. Conventional porous media simulations have difficulty analyzing the mass transfer law of small-scale models under the influence of microfractures. Based on the CT scanning data and thin section data of the real core in the target area, the rock skeleton and flow space were extracted according to the maximum ball algorithm, and the pore network model representing the complex structure was constructed. The microscale effect of macromolecules in the flow process in the pores was characterized by modifying the effective flow. The effects of the BLE on the effective connectivity, displacement process, and oil distribution law were analyzed. The seepage characteristics of different wettability conditions and different water cut stages were compared. The results show that BLE reduces the effective flow space and leads to deviations in the relative permeability curve and capillary curve. For fractured porous media, the irregular shape of porous media was characterized by the morphological method, and the mass transfer process was analyzed by the equivalent flux method. The influence of the porous media shape on the macromass transfer process was compared. This study provides a solution to the problem of BLE in pore-scale simulation.
Robust frequency diversity based algorithm for clutter noise reduction of ultrasonic signals using multiple sub-spectrum phase coherence

This paper presents a robust frequency diversity based algorithm for clutter reduction in ultrasonic A-scan waveforms. The performance of conventional spectral-temporal techniques like Split Spectrum Processing (SSP) is highly dependent on the parameter selection, especially when the signal to noise ratio (SNR) is low. Although spatial beamforming offers noise reduction with less sensitivity to parameter variation, phased array techniques are not always available. The proposed algorithm first selects an ascending series of frequency bands. A signal is reconstructed for each selected band in which a defect is present when all frequency components are in uniform sign. Combining all reconstructed signals through averaging gives a probability profile of potential defect position. To facilitate data collection and validate the proposed algorithm, Full Matrix Capture is applied on the austenitic steel and high nickel alloy (HNA) samples with 5MHz transducer arrays. When processing A-scan signals with unrefined parameters, the proposed algorithm enhances SNR by 20dB for both samples and consequently, defects are more visible in B-scan images created from the large amount of A-scan traces. Importantly, the proposed algorithm is considered robust, while SSP is shown to fail on the austenitic steel data and achieves less SNR enhancement on the HNA data.
Potamogeton perfoliatus L. Extract Attenuates Neuroinflammation and Neuropathic Pain in Sciatic Nerve Chronic Constriction Injury-Induced Peripheral Neuropathy in Rats

Sciatic nerve injury is often associated with neuropathic pain and neuroinflammation in the central and peripheral nervous systems. In our previous work, Potamogeton perfoliatus L. displayed anti-inflammatory, antipyretic and analgesic properties, predominantly via the inhibition of COX-2 enzyme and attenuation of oxidative stress. Herein, we extended our investigations to study the effects of the plant’s extract on pain-related behaviors, oxidative stress, apoptosis markers, GFAP, CD68 and neuro-inflammation in sciatic nerve chronic constriction injury (CCI) rat model. The levels of the pro-inflammatory marker proteins in sciatic nerve and brainstem were measured with ELISA 14 days after CCI induction. Pretreatment with the extract significantly attenuated mechanical and cold allodynia and heat hyperalgesia with better potential than the reference drug, pregabalin. In addition, CCI lead to the overexpression of prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), tumor necrosis alpha (TNFα), nuclear factor κB (NF-κB), cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX), and NADPH oxidase-1 (NOX-1) and decreased the catalase level in sciatic nerve and brainstem. The observed neuro-inflammatory changes were accompanied with glial cells activation (increased GFAP and CD68 positive cells), apoptosis (increased Bax) and structural changes in both brainstem and sciatic nerve. The studied extract attenuated the CCI-induced neuro-inflammatory changes, oxidative stress, and apoptosis while it induced the expression of Bcl-2 and catalase in a dose dependent manner. It also decreased the brainstem expression of CD68 and GFAP indicating a possible neuroprotection effect. Taking together, P. perfoliatus may be considered as a novel therapy for neuropathic pain patients after performing the required clinical trials.
Vascular Microenvironment, Tumor Immunity and Immunotherapy

Immunotherapy holds great promise for treating cancer. Nonetheless, T cell-based immunotherapy of solid tumors has remained challenging, largely due to the lack of universal tumor-specific antigens and an immunosuppressive tumor microenvironment (TME) that inhibits lymphocyte infiltration and activation. Aberrant vascularity characterizes malignant solid tumors, which fuels the formation of an immune-hostile microenvironment and induces tumor resistance to immunotherapy, emerging as a crucial target for adjuvant treatment in cancer immunotherapy. In this review, we discuss the molecular and cellular basis of vascular microenvironment-mediated tumor evasion of immune responses and resistance to immunotherapy, with a focus on vessel abnormality, dysfunctional adhesion, immunosuppressive niche, and microenvironmental stress in tumor vasculature. We provide an overview of opportunities and challenges related to these mechanisms. We also propose genetic programming of tumor endothelial cells as an alternative approach to recondition the vascular microenvironment and to overcome tumor resistance to immunotherapy.