bluuebunny/crossref_metadata_2025_split huggingface dataset:
The gut hormone Allatostatin C/Somatostatin regulates food intake and metabolic homeostasis under nutrient stress
Authors: Kubrak Olga , Koyama Takashi , Ahrentløv Nadja , Jensen Line , Malita Alina , Naseem Muhammad T. , Lassen Mette , Nagy Stanislav , Texada Michael J. , Halberg Kenneth V. , Rewitz Kim 
Published: February 2022

AbstractThe intestine is a central regulator of metabolic homeostasis. Dietary inputs are absorbed through the gut, which senses their nutritional value and relays hormonal information to other organs to coordinate systemic energy balance. However, the gut-derived hormones affecting metabolic and behavioral responses are poorly defined. Here we show that the endocrine cells of the Drosophila gut sense nutrient stress through a mechanism that involves the TOR pathway and in response secrete the peptide hormone allatostatin C, a Drosophila somatostatin homolog. Gut-derived allatostatin C induces secretion of glucagon-like adipokinetic hormone to coordinate food intake and energy mobilization. Loss of gut Allatostatin C or its receptor in the adipokinetic-hormone-producing cells impairs lipid and sugar mobilization during fasting, leading to hypoglycemia. Our findings illustrate a nutrient-responsive endocrine mechanism that maintains energy homeostasis under nutrient-stress conditions, a function that is essential to health and whose failure can lead to metabolic disorders.
High-precision and linear weight updates by subnanosecond pulses in ferroelectric tunnel junction for neuro-inspired computing
Authors: Luo Zhen , Wang Zijian , Guan Zeyu , Ma Chao , Zhao Letian , Liu Chuanchuan , Sun Haoyang , Wang He , Lin Yue , Jin Xi , Yin Yuewei , Li Xiaoguang 
Published: February 2022

AbstractThe rapid development of neuro-inspired computing demands synaptic devices with ultrafast speed, low power consumption, and multiple non-volatile states, among other features. Here, a high-performance synaptic device is designed and established based on a Ag/PbZr0.52Ti0.48O3(PZT, (111)-oriented)/Nb:SrTiO3ferroelectric tunnel junction (FTJ). The advantages of (111)-oriented PZT (~1.2 nm) include its multiple ferroelectric switching dynamics, ultrafine ferroelectric domains, and small coercive voltage. The FTJ shows high-precision (256 states, 8 bits), reproducible (cycle-to-cycle variation, ~2.06%), linear (nonlinearity <1) and symmetric weight updates, with a good endurance of >109cycles and an ultralow write energy consumption. In particular, manipulations among 150 states are realized under subnanosecond (~630 ps) pulse voltages ≤5 V, and the fastest resistance switching at 300 ps for the FTJs is achieved by voltages <13 V. Based on the experimental performance, the convolutional neural network simulation achieves a high online learning accuracy of ~94.7% for recognizing fashion product images, close to the calculated result of ~95.6% by floating-point-based convolutional neural network software. Interestingly, the FTJ-based neural network is very robust to input image noise, showing potential for practical applications. This work represents an important improvement in FTJs towards building neuro-inspired computing systems.
ROCK1 mechano-signaling dependency of human malignancies driven by TEAD/YAP activation
Authors: Esposito Davide , Pant Ila , Shen Yao , Qiao Rui F. , Yang Xiaobao , Bai Yiyang , Jin Jian , Poulikakos Poulikos I. , Aaronson Stuart A. 
Published: February 2022

AbstractRho family mechano-signaling through the actin cytoskeleton positively regulates physiological TEAD/YAP transcription, while the evolutionarily conserved Hippo tumor suppressor pathway antagonizes this transcription through YAP cytoplasmic localization/degradation. The mechanisms responsible for oncogenic dysregulation of these pathways, their prevalence in tumors, as well as how such dysregulation can be therapeutically targeted are not resolved. We demonstrate that p53 DNA contact mutants in human tumors, indirectly hyperactivate RhoA/ROCK1/actomyosin signaling, which is both necessary and sufficient to drive oncogenic TEAD/YAP transcription. Moreover, we demonstrate that recurrent lesions in the Hippo pathway depend on physiological levels of ROCK1/actomyosin signaling for oncogenic TEAD/YAP transcription. Finally, we show that ROCK inhibitors selectively antagonize proliferation and motility of human tumors with either mechanism. Thus, we identify a cancer driver paradigm and a precision medicine approach for selective targeting of human malignancies driven by TEAD/YAP transcription through mechanisms that either upregulate or depend on homeostatic RhoA mechano-signaling.
The effect of stress and exercise on the learning performance of horses
Authors: Henshall Cathrynne , Randle Hayley , Francis Nidhish , Freire Rafael 
Published: February 2022

AbstractDomestic horses are widely used for physically demanding activities but the effect of exercise on their learning abilities has not been explored. Horses are also frequently exposed to stressors that may affect their learning. Stress and exercise result in the release of glucocorticoids, noradrenaline and other neurotransmitters that can influence learning. It is not currently possible to directly measure concentrations of neurotransmitters in the brains of behaving horses, however the inference of neurobiological processes from peripheral markers have been widely used in studies of human cognition. We assigned 41 horses to either ridden exercise, uncontrollable stress or inactivity and evaluated their acquisition of an industry-style aversive instrumental learning task. Exercised horses achieved the learning criterion in the fewest number of trials compared to the stressed and inactive horses whose performance did not differ. The exercised horses’ salivary cortisol concentrations decreased during learning whereas the concentrations of the other groups increased. Spearman’s correlations revealed that horses with the highest cortisol concentrations required the most trials to reach the criterion. We present novel data that exercise prior to learning may enhance the acquisition of learning in horses. Conversely, activities that expose horses to uncontrollable stressors causing strong cortisol release may impair learning. It is proposed that these effects may be due to the influence of neurotransmitters such as cortisol and noradrenaline on brain regions responsible for learning.
Ionic mitigation of CD4+ T cell metabolic fitness, Th1 central nervous system autoimmunity and Th2 asthmatic airway inflammation by therapeutic zinc
Authors: Krone Anna , Fu Yan , Schreiber Simon , Kotrba Johanna , Borde Loisa , Nötzold Aileen , Thurm Christoph , Negele Jonas , Franz Tobias , Stegemann-Koniszewski Sabine , Schreiber Jens , Garbers Christoph , Shukla Aniruddh , Geffers Robert , Schraven Burkhart , Reinhold Dirk , Dudeck Anne , Reinhold Annegret , Müller Andreas J. , Kahlfuss Sascha 
Published: February 2022

AbstractT helper (Th) cells provide immunity to pathogens but also contribute to detrimental immune responses during allergy and autoimmunity. Th2 cells mediate asthmatic airway inflammation and Th1 cells are involved in the pathogenesis of multiple sclerosis. T cell activation involves complex transcriptional networks and metabolic reprogramming, which enable proliferation and differentiation into Th1 and Th2 cells. The essential trace element zinc has reported immunomodulatory capacity and high zinc concentrations interfere with T cell function. However, how high doses of zinc affect T cell gene networks and metabolism remained so far elusive. Herein, we demonstrate by means of transcriptomic analysis that zinc aspartate (UNIZINK), a registered pharmaceutical infusion solution with high bioavailability, negatively regulates gene networks controlling DNA replication and the energy metabolism of murine CD3/CD28-activated CD4+ T cells. Specifically, in the presence of zinc, CD4+ T cells show impaired expression of cell cycle, glycolytic and tricarboxylic acid cycle genes, which functionally cumulates in reduced glycolysis, oxidative phosphorylation, metabolic fitness and viability. Moreover, high zinc concentrations impaired nuclear expression of the metabolic transcription factor MYC, prevented Th1 and Th2 differentiation in vitro and reduced Th1 autoimmune central nervous system (CNS) inflammation and Th2 asthmatic airway inflammation induced by house dust mites in vivo. Together, we find that higher zinc doses impair the metabolic fitness of CD4+ T cells and prevent Th1 CNS autoimmunity and Th2 allergy.
The influence of CD26+ and CD26− fibroblasts on the regeneration of human dermo-epidermal skin substitutes
Authors: Michalak-Micka Katarzyna , Klar Agnes S. , Dasargyri Athanasia , Biedermann Thomas , Reichmann Ernst , Moehrlen Ueli 
Published: February 2022

AbstractCD26, also known as dipeptidyl peptidase IV (DPPIV), is a multifunctional transmembrane protein playing a significant role in the cutaneous wound healing processes in the mouse skin. However, only scarce data are available regarding the distribution and function of this protein in the human skin. Therefore, the aim of this study was to investigate the impact of CD26 deficiency in human primary fibroblasts on the regeneration of human tissue-engineered skin substitutes in vivo. Dermo-epidermal skin analogs, based on collagen type I hydrogels, were populated either with human CD26+ or CD26knockout fibroblasts and seeded with human epidermal keratinocytes. These skin substitutes were transplanted onto the back of immune-incompetent rodents. Three weeks post-transplantation, the grafts were excised and analyzed with respect to specific epidermal and dermal maturation markers. For the first time, we show here that the expression of CD26 protein in human dermis is age-dependent. Furthermore, we prove that CD26+ fibroblasts are more active in the production of extracellular matrix (ECM) both in vitro and in vivo and are necessary to achieve rapid epidermal and dermal homeostasis after transplantation.
Infrared- and white-light retinal sensitivity in glaucomatous neuropathy
Authors: Łabuz Grzegorz , Rayamajhi Asu , Komar Katarzyna , Khoramnia Ramin , Auffarth Gerd U. 
Published: February 2022

AbstractGlaucoma causes irreversible neuropathy, which, untreated, may lead to blindness. In this case–control study, we measured two-photon infrared (IR) light sensitivity in glaucomatous eyes to propose a new method to quantify the visual loss. In total, 64 patients were recruited with an equal distribution between glaucoma and control groups. Retinal sensitivity to IR light was assessed using a two-photon excitation device. A fundus-driven microperimeter was used to measure retinal sensitivity to visible light. The retinal nerve fiber layer (RNFL) thickness was quantified automatically with optical coherence tomography. The IR sensitivity of glaucoma and control eyes differed significantly (P = .003): 9.8 (6.5 to 13.1) dB vs. 10.9 (8.2 to 13.0) dB. Although in the visible-light microperimetry, retinal sensitivity was decreased in glaucoma (17.0, range: 6.9 to 20.0 dB) compared to the controls (17.7, range: 11.6 to 20.0 dB), this difference did not reach the significance level. A significant thinning of the RNFL in the glaucoma group was observed (P < .001). IR sensitivity significantly correlated with the RNFL in three of the four assessed quadrants instead of only one in visible-light microperimetry. Although further research is needed, this proof-of-concept study suggests that IR-light sensitivity can be used to support the detection of glaucomatous neuropathy.
Prognostic value of Dickkopf-1 and ß-catenin expression according to the antitumor immunity of CD8-positive tumor-infiltrating lymphocytes in biliary tract cancer
Authors: Kim Seo Ree , Won Hye Sung , Yang Ji Hyun , Sun Der Sheng , Yim Kwangil , Hong Mineui , Hong Soon Auck , Yoon Jung-Sook , Chun Sang Hoon , Kim Kee-Hwan , Ko Yoon Ho 
Published: February 2022

AbstractThe role of β-catenin and Dickkopf-1 (DKK1) is dependent on the specific immunobiology of T cell inflammation in biliary tract cancer (BTC). We aimed to analyze the role of DKK1 or β-catenin as a prognostic factor in BTC, and determine the clinical associations of ß-catenin and DKK1 with CD8+ tumor-infiltrating lymphocytes (TIL). We used data from The Cancer Genome Atlas Research Network and the clinicopathological data of 145 patients with BTC who had undergone primary radical resection between 2006 and 2016. CD8+ TIL expression was a significant predictor of favorable overall survival (OS) and relapse-free survival (RFS) (median OS, 34.9 months in high-TIL, 16.7 months in low-TIL, P < 0.0001 respectively; median RFS, 27.1 months in high-TIL, 10.0 months in low-TIL, P < 0.0001 respectively). In the high-CD8+ TIL BTC group, the tumor expression of β-catenin and DKK1 had a significant negative impact on either OS or RFS. In the low-TIL BTC group, there were no differences according to ß-catenin and DKK1 expression. Cox regression multivariate analysis demonstrated that CD8+ TIL and β-catenin retained significant association with OS. Among patients with resected BTC, the β-catenin and DKK1 protein and high CD8+ TIL levels were associated with poor and good clinical outcomes, respectively.
Systematic evaluation of the prognostic and immunological role of PDLIM2 across 33 cancer types
Authors: Zeng Yudan , Lin Dongtao , Gao Mengqian , Du Guoxia , Cai Yongming 
Published: February 2022

AbstractThe protein PDLIM2 regulates the stability of various transcription factors and is required for polarized cell migration. However, the clinical relevance and immune infiltration of PDLIM2 in cancer are not well-understood. We utilized The Cancer Genome Atlas and Genotype-Tissue Expression database to characterize alterations in PDLIM2 in pan-cancer. TIMER was used to explore PDLIM2 expression and immune infiltration levels. We assessed the correlation between PDLIM2 expression and immune-associated gene expression, immune score, tumor mutation burden, and DNA microsatellite instability. PDLIM2 significantly affected the prognosis of various cancers. Increased expression of PDLIM2 was significantly correlated with the tumor grade in seven types of tumors. The expression level of PDLIM2 was positively correlated with immune infiltrates, including B cells, CD8+ T cells, CD4+ T cells, neutrophils, macrophages, and dendritic cells in bladder urothelial, kidney renal papillary cell, and colon adenocarcinoma. High expression levels of PDLIM2 tended to be associated with higher immune and stromal scores. PDLIM2 expression was associated with the tumor mutation burden in 12 cancer types and microsatellite instability in 5 cancer types. PDLIM2 levels were strongly correlated with diverse immune-related genes. PDLIM2 can act as a prognostic-related therapeutic target and is correlated with immune infiltrates in pan-cancer.
Identification and evaluation of the effective criteria for detection of congestion in a smart city
Authors: Mohanty Anita , Mohanty Subrat Kumar , Jena Bhagyalaxmi , Mohapatra Ambarish G. , Rashid Ahmed N. , Khanna Ashish , Gupta Deepak 
Published: February 2022

AbstractThe delay in transportation of necessary items is due to traffic congestion throughout the world. This is a serious phenomenon which results in waste of time and fuel. The detection of road conditions and dissemination of traffic information efficiently and effectively is a big challenge to authorities. Recently, the technologies of vehicular ad hoc networks (VANETs) have been utilized and become an important part of the intelligent transportation system (ITS). For this existing problem, vehicle‐to‐vehicle (V2V) communication provides a means for cooperation and route management in transport networks. This paper proposed a novel congestion detection system based on the combination of k‐means clustering and analytical hierarchy process. In the simulation of urban mobility (SUMO) simulator, a transport network is created and parameters of vehicles facing congestion are taken to extract the key parameter by using the k‐means clustering technique and mathematical mean algorithm. This parameter is utilized in analytical hierarchy process to detect the highest priorities parameter and based on that the congestion is detected in particular lane. The result can be a better technique for congestion detection as it requires low installation cost and can be incorporate in vehicles for congestion avoidance which will alternatively improve the traffic flow.
A novel protection and fault location combined algorithm for mixed/hybrid lines
Authors: Aminirad Mohammad , Shahrtash S. Mohammad 
Published: February 2022

AbstractThis paper presents a novel protection and fault location combined algorithm for mixed overhead transmission lines (OHLs) and underground cables (UGCs). The method is based on applying the Morphological Gradient (MG) to the modal component of synchronized measured currents at both ends of the mixed line to detect the transient components generated by the fault. The proposed method utilizes the sign of superimposed components for discriminating internal and external faults and the difference between the times related to these transient components to detect fault location. The method has been evaluated through various simulations, whereas it has a very low computational burden, it is suitable for online applications. Results have shown high performance of the method against different fault inception angles (FIA), fault resistances, fault types, fault locations, combinations of OHL‐UGC, and even current transformer saturation, noise presence, long cable section, and different sheath‐ground connections.
An extendable single‐input reduced‐switch 11‐level switched‐capacitor inverter with quintuple boosting factor
Authors: Deliri Saeid , Varesi Kazem , Padmanaban Sanjeevikumar 
Published: February 2022

AbstractThis paper proposes a novel single‐phase switched‐capacitor‐based inverter configuration that in its basic form can generate an 11‐level staircase output voltage waveform with sinusoidal output current for Resistive‐Inductive (R‐L) loads. The increased levels, quintuple voltage‐boosting factor, and natural voltage‐balancing of capacitors are considered the main features of the proposed basic configuration. The proposed topology requires fewer components (resources, switches, driver circuits, and capacitors) than recently presented similar structures to acquire the same voltage gain and output steps. The proposed basic configuration can be extended in two ways: increasing levels and/or boosting factors with minimal devices. The employment of two half‐bridges (rather than an H‐bridge) for generating bipolar waveform has limited the number of switches tolerating the maximum output voltage to 2 (instead of 4), which results in reduced total blocking voltage (TBV) and accordingly reduced cost and losses. A comprehensive comparative analysis has been done and presented to verify the supremacy of the suggested structure. The experimental results of the laboratory‐scaled prototype of the proposed basic topology have been provided, which approve its correct performance.
Effective identification of distributed energy resources using smart meter net‐demand data
Authors: Moreno Jaramillo Andres F. , Lopez‐Lorente Javier , Laverty David M. , Martinez‐del‐Rincon Jesus , Morrow D. John , Foley Aoife M. 
Published: February 2022

AbstractInternational policies and targets to globally reduce carbon dioxide emissions have contributed to increasing penetration of distributed energy resources (DER) in low‐voltage distribution networks. The growth of technologies such as rooftop photovoltaic (PV) systems and electric vehicles (EV) has, to date, not been rigorously monitored and record keeping is deficient. Non‐intrusive load monitoring (NILM) methods contribute to the effective integration of clean technologies within existing distribution networks. In this study, a novel NILM method is developed for the identification of DER electrical signatures from smart meter net‐demand data. Electrical profiles of EV and PV systems are allocated within aggregated measurements including conventional electrical appliances. Data from several households in the United States are used to train and test classification and regression models. The usage of conventional machine learning techniques provides the proposed algorithm with fast processing times and low system complexity, key factors needed to differentiate highly variable DER power profiles from other loads. The results confirm the effectiveness of the proposed methodology to individually classify DER with performance metrics of 96% for EV and 99% for PV. This demonstrates the potential of the proposed method as an embedded function of smart meters to increase observability in distribution networks.
The Role of Tissue-Nonspecific Alkaline Phosphatase in Dental Tissue:
A Review of Recent Literature
Authors: Graser Stephanie , Riekert Elisa , Liedtke Daniel 
Published: February 2022

AbstractThis brief review describes the role of tissue-nonspecific alkaline phosphatase
(TNAP) during dental development. Mutations within the ALPL gene, which is
encoding the human ectoenzyme TNAP, lead to the rare disease Hypophosphatasia
(HPP). Apart from the most prominent bone hypomineralization, the characteristic
symptoms of HPP often include a dental phenotype. To investigate the molecular
causes of distinct HPP symptoms in closer detail, a number of transgenic models
in different animals are established, like mice (Mus musculus) and
zebrafish (Danio rerio). We therefore also compare the processes of
dental development in humans, mice, and zebrafish.
Embryologic and Fetal Development of the Eyelid and the Lacrimal
Drainage System
Authors: Gaca Piotr Jakub , Lewandowicz Michael , Lipczynska-Lewandowska Malgorzata , Simon Michael , Matos Philomena A. Wawer , Doulis Alexandros , Rokohl Alexander C. , Heindl Ludwig M. 
Published: February 2022

AbstractThe embryological and fetal morphogenesis of the eyelids and lacrimal drainage
system is multifactorial and complex. This protracted process begins in the 5th
week of prenatal life and involves a successive series of subtle and tightly
regulated morphogenetic events. Major milestones of the embryological and fetal
development of the eyelids include the beginning of eyelid formation during the
6th week, eyelid fusion by the 8th week, and the development of eyelid
structures beginning in the 9th week (immediately following eyelid fusion), with
progression until eyelid separation by the 24th week. After eyelid separation,
the eyelids begin to assume their newly developed shape. Around the 32nd week,
eyelids are almost fully developed and fully separated but still visibly closed.
Key development steps of the lacrimal drainage system include formation of the
lacrimal lamina (the primordium of the future lacrimal system) and the lacrimal
cord (the primordium of the lacrimal canaliculi) in the 7th week, with
canalization starting from the 10th week. During the 10th week, the excretory
lacrimal system displays a lumen with a true lacrimal duct that can be
distinguished. The epithelium of the lacrimal canaliculi is in contact with the
palpebral conjunctival epithelium. The two epithelia form a continuous
epithelial lamina. The caudal extreme of the lacrimal duct and the inferior
meatal lamina join and the latter begins to cavitate. Understanding this
multidimensional process of development in prenatal life, as well as identifying
and linking signaling cascades and regulatory genes to existing diseases, may
pave the way for developing minimally invasive interventions and scar reducing
surgical methods, controlling the spread of malignancies, and the use of
progenitor/stem cell and even regenerative therapy.