bluuebunny/crossref_metadata_2025 huggingface dataset:
PGK1 contributes to tumorigenesis and sorafenib resistance of renal clear cell carcinoma via activating CXCR4/ERK signaling pathway and accelerating glycolysis
Authors: He Yu , Wang Xixi , Lu Weiliang , Zhang Dan , Huang Lan , Luo Yang , Xiong Li , Li Haocheng , Zhang Peng , Li Qiu , Liang Shufang
Published: February 2022

Phosphoglycerate kinase 1 (PGK1) has complicated and multiple functions in cancer occurrence, tumor progression and drug resistance. Sorafenib is the first-line treatment targeted drug for patients with kidney renal clear cell carcinoma (KIRC) as a tyrosine kinase inhibitor, but sorafenib resistance is extremely common to retard therapy efficiency. So far, it is unclear whether and how PGK1 is involved in the pathogenesis and sorafenib resistance of KIRC. Herein, the molecular mechanisms of PGK1-mediated KIRC progression and sorafenib resistance have been explored by comprehensively integrative studies using biochemical approaches, mass spectrometry (MS) identification, microarray assay, nude mouse xenograft model and bioinformatics analysis. We have confirmed PGK1 is specifically upregulated in KIRC based on the transcriptome data generated by our own gene chip experiment, proteomics identification and the bioinformatics analysis for five online transcriptome datasets, and PGK1 upregulation in tumor tissues and serum is indicative with poor prognosis of KIRC patients. In the KIRC tissues, a high expression of PGK1 is often accompanied with an increase of glycolysis-related enzymes and CXCR4. PGK1 exhibits pro-tumorigenic properties in vitro and in a xenograft tumor model by accelerating glycolysis and inducing CXCR4-mediated phosphorylation of AKT and ERK. Moreover, PGK1 promotes sorafenib resistance via increasing CXCR4-mediated ERK phosphorylation. In conclusion, PGK1-invovled metabolic reprogramming and activation of CXCR4/ERK signaling pathway contributes to tumor growth and sorafenib resistance of KIRC.
Tumour cell apoptosis modulates the colorectal cancer immune microenvironment via interleukin-8-dependent neutrophil recruitment
Authors: Schimek Vanessa , Strasser Katharina , Beer Andrea , Göber Samantha , Walterskirchen Natalie , Brostjan Christine , Müller Catharina , Bachleitner-Hofmann Thomas , Bergmann Michael , Dolznig Helmut , Oehler Rudolf
Published: February 2022

Sporadic apoptosis of tumour cells is a commonly observed feature of colorectal cancer (CRC) and strongly correlates with adverse patient prognosis. The uptake of apoptotic cell debris by neutrophils induces a non-inflammatory, pro-regenerative, and hence potentially pro-tumorigenic phenotype. In this study, we therefore sought to investigate the impact of apoptotic CRC cells on neutrophils and its consequence on other immune cells of the tumour microenvironment. Apoptosis induced by combined TNFα-treatment and UV-C irradiation, as well as various chemotherapeutic agents, led to a substantial release of neutrophil-attracting chemokines, most importantly interleukin-8 (IL-8), in both primary patient-derived and established CRC cells. Accordingly, conditioned media of apoptotic tumour cells selectively stimulated chemotaxis of neutrophils, but not T cells or monocytes. Notably, caspase-inhibition partially reduced IL-8 secretion, suggesting that caspase activity might be required for apoptosis-induced IL-8 release. Moreover, apoptotic tumour cell-conditioned media considerably prolonged neutrophil lifespan and induced an activated CD66bhighCD11bhighCD62Llow phenotype, comparable to that of tumour-associated neutrophils in CRC patients, as assessed by flow cytometry of dissociated CRC tissues. Immunohistochemical analyses of 35 CRC patients further revealed a preferential accumulation of neutrophils at sites of apoptotic tumour cells defined by the expression of epithelial cell-specific caspase-cleaved cytokeratin-18. The same areas were also highly infiltrated by macrophages, while T cells were virtually absent. Notably, neutrophils induced an M2-like CD86lowCD163+CD206+ phenotype in co-cultured monocyte-derived macrophages and suppressed LPS-induced pro-inflammatory cytokine release. In an in vitro transwell model, IL-8 blockade efficiently prevented neutrophil-induced anti-inflammatory macrophage polarisation by inhibiting neutrophil migration towards IL-8 gradients generated by apoptotic CRC cells. To conclude, our data suggest that apoptotic cancer cells release chemotactic factors that attract neutrophils into the tumour, where their interaction with neighbouring macrophages might promote an immunologically unfavourable tumour microenvironment. This effect may contribute to tumour recurrence after chemotherapy-induced apoptosis.
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

The 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

The 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

Rho 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

Domestic 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

T 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

CD26, 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

Glaucoma 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

The 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

The 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.
Effective and simple removal of Hg from real waters by a robust bio-nanocomposite
Authors: Domingues Eddy M. , Gonçalves Gil , Henriques Bruno , Pereira Eduarda , Marques Paula A. A. P.
Published: February 2022

The purpose of this study is to immobilize GOPEI on a spongin skeleton coated with an alginate coating layer in order to generate a cohesive composite that is very efficient in removing Hg and can be easily recovered from remediated water.
Effect of polysaccharides from Tibetan turnip (Brassica rapaL.) on the gut microbiome afterin vitrofermentation andin vivometabolism
Authors: Liu Lin , Liu Chang , Hua Hanyi , Zhao Wenjin , Zhu Hongkang , Cheng Yuliang , Guo Yahui , Qian He
Published: February 2022

Tibetan turnip polysaccharide (TTP) was undigested after gastrointestinal-digestion. TTP fermentationin vivoandin vitrocould produce short-chain fatty acids and change the composition of the intestinal flora.
Synthesis of carboxylic acids via the hydrocarboxylation of alcohols with CO2 and H2
Authors: Zhang Yanru , Wang Ying , Qian Qingli , Li Yang , Asare Bediako Bernard Baffour , Zhang Jingjing , Yang Junjuan , Li Zhiyan , Han Buxing
Published: February 2022

Alcohols with different chain lengths can react with CO2 and H2 to produce C1-elongated carboxylic acids using an Ir catalyst.
Fabrication of solution-processable OFET memory using a nano-floating gate based on a phthalocyanine-cored star-shaped polymer
Authors: Aimi Junko , Yasuda Takeshi , Huang Chih-Feng , Yoshio Masafumi , Chen Wen-Chang
Published: February 2022

A simple one-pot solution-processed OFET memory device has been fabricated based on the vertical phase separation of phthalocyanine-cored star-shaped polystyrene and an organic semiconductor.
Realizing shape and size control for the synthesis of coordination polymer nanoparticles templated by diblock copolymer micelles
Authors: Göbel Christoph , Marquardt Katharina , Baabe Dirk , Drechsler Markus , Loch Patrick , Breu Josef , Greiner Andreas , Schmalz Holger , Weber Birgit
Published: February 2022

The combination of block polymers with nanoparticles offers the possibility to obtain customizable composite materials with additional properties such as sensing or bistability provided by a switchable spin crossover (SCO) core.
A dual-mode laser-textured ice-phobic slippery surface: low-voltage-powered switching transmissivity and wettability for thermal management
Authors: Chen Chao , Chen Yan , Yao Hao , Song Qingrui , Jia Chong , Zhang Yachao
Published: February 2022

An electric-triggered dual-mode slippery liquid infused surface enabled by ultra-fast laser is reported for solving challenges in integrating anti-icing, self-cleaning and light-regulating functionalities into a single device.
Triple captured iron by defect abundant NiO for efficient water oxidation
Authors: Zhou Ya-Nan , Wang Feng-Ge , Zhou Jian-Cheng , Dong Bin , Dong Yi-Wen , Liu Xin , Liu Bin , Yu Jian-Feng , Chai Yong-Ming
Published: February 2022

Fe-doped NiO host (Fe–NiMoO4@NiO-30) with a large surface area is designed to achieve the triple capture of Fe via adjustable surface reconstruction and impregnation to optimize the OER activity and durability of bimetallic NiFe hydroxides.
Dynamic role of the correlation effect revealed in the exceptionally slow autodetachment rates of the vibrational Feshbach resonances in the dipole-bound state
Authors: Kang Do Hyung , Kim Jinwoo , Kim Sang Kyu
Published: February 2022

Exceptionally slow autodetachment dynamics of the vibrational Feshbach resonances found in the dipole-bound state of 4-bromophonoxide (4-BrPhO−) or 4-chlorophenoxide (4-ClPhO−) anions reveals the associated dynamic role of the correlation effect.
Mechanism of diastereoisomer-induced chirality of BiOBr
Authors: Ding Kun , Ai Jing , Duan Yingying , Han Lu , Qu Zhibei , Che Shunai
Published: February 2022

The chirality transfer is dependent on geometrical matching between the chiral inducer and inorganic species.
Circumferential Li metal deposition at high rates enabled by the synergistic effect of a lithiophilic and ionic conductive network
Authors: Zheng Nan , Liang Chao , Wu Cong , Zhang Xun , Zhai Wenbo , Liu MingXian , Wei Hengsheng , Zhang Chang , Dong Lei , Yu Yi , Liu Wei , Yao Lei
Published: February 2022

LLTO/C composites form fast Li+ diffusion paths. The lithiophilic Au layer coated on LLTO/C improves the surface lithiophilicity and further accelerates Li+ diffusion, realizing uniform Li metal deposition at high rates.
Recent progress in all-small-molecule organic photovoltaics
Authors: Xu Chunyu , Zhao Zijin , Yang Kaixuan , Niu Lianbin , Ma Xiaoling , Zhou Zhengji , Zhang Xiaoli , Zhang Fujun
Published: February 2022

This review systematically summarizes the development of all-small-molecule organic photovoltaics (SMPVs) from molecule engineering and device engineering aspects, and highlights the challenges and perspectives of further developing SMPVs.
A predictive model of surface adsorption in dissolution on transition metals and alloys
Authors: Li Bo , Li Xin , Gao Wang
Published: February 2022

A predictive model is established to determine adsorption energy in dissolution on TMs and alloys by using the electronic gradient and cohesive energy of surface sites, which builds a novel physical picture for surface adsorption on alloys.
Variable-valence ion and heterointerface accelerated electron transfer kinetics of electrochemical water splitting
Authors: Lu Mengfei , Kong Shaoxi , Yan Shicheng , Zhou Peng , Yu Tao , Zou Zhigang
Published: February 2022

The electron transfer from OER intermediates via the amorphous NiFeOOH shell was efficiently accelerated by the variable-valence V3+/4+ acceptor at core@shell interface and the heterojunction effect in Ni3Fe1−xVx/Ni3Fe1−xVxN core, significantly facilitating the OER performance.
An efficient Cu2Zn1−xInxSn(S,Se)4 multicomponent photocathode via one-step hydrothermal approach for thin film solar cell
Authors: Patil Satish S. , Nadaf Sameer N. , Khot Kishorkumar V. , Mane Rahul M. , Mohite Suhas S. , Mali Sawanta S. , Hong Chang Kook , Bhosale Popatrao N.
Published: February 2022

In the present study, a facile hydrothermal route was successfully implemented for the synthesis of Cu2Zn1−xInxSn(S,Se)4 (x = 0.0 to 0.075 M) (CZITSSe) thin films for solar cells.
Government science ambitions require greater funding and wider public understanding
Authors: Taylor Ian
Published: February 2022

Following the outbreak of COVID-19 and facing the challenges and opportunities of a post-Brexit world, the UK government must deliver on the vision of its innovation strategy with increased funding for scientific research. The success of the life sciences sector will be key to the delivery of the government’s scientific superpower ambitions. Boosting public funding will depend on continued political, and therefore public, support. With reference to his career in politics and industry, Ian Taylor shows how effective communication with the public, providing reassurance and dispelling myths, is central to the sector sustaining success in the long term.
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

The 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

This 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

This 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

International 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.
Dynamic viscosity, centrifugation test and kinetic investigation in emulsions with pumpkin oil
Authors: Gandova Vanya , Petrova Ivalina , Tasheva Stanislava , Stoyanova Albena
Published: February 2022

The emulsion stability of different pumpkin O/W emulsions was investigated. Preparation of emulsions were performed with oil phase between 10 and 40 percent, water and soybean protein isolate. To determine emulsion properties different methods were used. Density, viscosity, centrifugation tests and spectroscopic measurements were performed for their investigations. The emulsions were stored for two weeks to determine their kinetic. Influence of the oil phase was presented and connected with the stability of them.
Evaluation of the qualitative parameters of raw sheep’s milk with the potential for the production of traditional artisanal cheese
Authors: Stankov Stanko , Fidan Hafize , Balabanova Tatyana , Dimitrova Eva , Ibrahim Salam A.
Published: February 2022

The aim of the present study was to investigate the physicochemical and microbiological profile of indigenous sheep’s milk with the potential for the production of artisanal cheese. The data showed the changes in lactation stages (between April and August) up to 2 hours following manual milk production. The quality of raw milk in the production of brined cheese using traditional technology was assessed. The amount of dry matter was21.36% in April and 19.85% in August at the end of lactation. The fat content from April to August was between 8.62% and 8.03%, preserving the values reported. The protein composition of raw milk varied between 5.52 – 6.61%. In the microbiological evaluation of raw sheep’s milk after milking (35.3°C), the total microbial contamination was in the range of 1.3 x 106to 1.4 x 106CFU/mL under current conditions. The results obtained in this paper give rise to more in-depth studies on the application of raw sheep’s milk in the production of traditional artisanal cheeses.
Effects of lingonberry extract (Vaccinium vitis-idaea L.) on the antioxidant, physicochemical and sensory characteristics of ice cream
Authors: Boyanova Petya , Gradinarska Dilyana , Dobreva Valentina , Ivanov Ivan , Petkova Nadejda
Published: February 2022

In the present work, ice cream mixtures with 5%, 10% and 15% lingonberry extract were studied. The lingonberry (Vaccinium vitis-idaea L.) is a source of anthocyanins and flavonoids, which are the bioactive components with good antioxidant properties. There was a significant increase in antioxidant activity (p<0.05) from 133.3 ± 5.6 mM TE/100 g to 249.8 ± 8.3 mM TE/100 g (ABTS method) with increasing the concentration of the extract from 5% to 15%, respectively. Significant changes (p<0.05) in the acidity and dry matter of the samples with lingonberry extract were recorded. After 30 days of storage, a decrease in the antioxidant properties (p<0.05) of the ice cream samples was observed but higher values (mM TE/100 g) were maintained compared to the sample without extract. The color characteristics of the samples were also influenced by the concentration of the extract used. During storage, the highest stability of the colorimetric index a* (red component) was established, which indicates relative color stability during storage.
Effect of Spirulina platensis on the quality and antioxidants characteristics of ice cream
Authors: Boyanova Petya , Gradinarska Dilyana , Dobreva Valentina , Panayotov Petar , Momchilova Maria , Zsivanovits Gabor
Published: February 2022

Spirulina platensis is a cyanobacterium (blue-green algae) that grows in alkaline waters. In food industry, Spirulina’s phycocyanin is used as a natural colorant and stabilizer. The influence of three different concentrations of Spirulina platensis (0.5%, 1% and 1.5%) on physicochemical, textural, antioxidant and sensory parameters of ice cream was studied. It was found that with increasing spirulina concentration, the overrun increases from 30.6% (IC–0) to 48.3% (IC–3). The analysis of texture profile (hardness, adhesiveness, cohesiveness, gumminess) of samples showed a statistically significant difference (p<0.05) between reported values for control sample (IC–0) and the samples with spirulina. Ice cream samples supplemented with spirulina differed with significant increase (p<0.05) in antioxidant activity from 2.8±2.2 mM TE/100 g DW (control sample) to 112.9±4.1 mM TE/100 g DW (IC–3). The addition of Spirulina platensis in ice cream mixture improves its quality and antioxidant properties.
Study on the effect of sublethal concentrations of antimicrobials on the growth and development of probiotic lactobacilli
Authors: Ilyazova Ayla , Blazheva Denica , Slavchev Aleksandar , Krastanov Albert
Published: February 2022

The objective of this study was to investigate the effect of sublethal concentrations of 5 antibiotics (tetracycline, erythromycin, penicillin G, lincomycin, ciprofloxacin) and 2 preservatives (benzoic and sorbic acid) on the growth and development of 8 probiotic Lactobacillus strains. All lactobacilli were subjected to a large range of concentrations, growth curves were plotted and MICs were determined for each antimicrobial. The results showed correlation between the sublethal concentrations and the growth rate of the studied microorganisms. Based on the obtained data two groups of strains could be defined – sensitive and relatively resistant. The first group includes L. bulgaricus S2. L. bulgaricus S4. L. bulgaricus S19 and L. gasseri S20. The most resistant of this group was L. gasseri S20. The second group showed more sensitivity and the most affected by the antimicrobials was L. bulgaricus S28.
Comparative study of DNA extraction methods for identification of medicinal mushrooms
Authors: Stefanova Petya , Brazkova Mariya , Angelova Galena
Published: February 2022

The isolation of high quantity and intact DNA is of a great significance for molecular identification of higher fungi. The aim of this study was to compare two DNA extraction methods for isolation of DNA from medicinal mushrooms of Agaricomycetes class. A modified CTAB method and a modified SDS method were compared by the yield and purity of the extracted DNA, its fragmentation state and suitability for amplification. The results demonstrated high efficiency of both methods in regard to DNA yield (14.18 -144.28 ng DNA/mg biomass with CTAB method and 15.03 -108.34 ng DNA/mg biomass with SDS method). The CTAB method provided DNA extracts with higher purity (A260/A280 ranged from 1.83 to 1.99) in comparison with the SDS method (A260/A280 = 1.53 -1.86). The modified CTAB method produced amplifiable DNA from all mushroom isolates, while the SDS method demonstrated suitability for amplification only in 50% of the samples. Therefore, the modified CTAB method could be the method of choice for DNA extraction from medicinal mushrooms. The analyzed isolates were subjected to molecular identification by ITS1-5.8S-ITS2 rRNA gene sequence analysis and were identified as Ganoderma resinaceum, Trametes versicolor, Fomitopsis pinicola and Inonotus hispidus.
Increasing fish diversity of Chicago's waterways
Authors: Happel Austin
Published: February 2022

Descriptions of shifts in biodiversity across time are desired for urban freshwater systems to better study ecosystem change and causal mechanisms. I document changes in fish diversity within the Chicago Area Waterways across 35 years using a battery of diversity metrics calculated on both abundance and biomass data. Has diversity of Chicago's waterways changed over 35 years and if so, do different diversity metrics exhibit different trends or breakpoints in trends? Diversity of the fish assemblage increased across the three decades of study. Breakpoint analysis suggested that trends across the timeseries were nonlinear. Changes in dominant species influenced behavior of less traditional metrics, whereas Margalef's Richness, Shannon-Weiner, and Gini-Simpson appeared more robust. Increases in richness and taxonomic diversity combined with decreases in species dominance suggest an ecosystem of increasing quality. The fish community of the Chicago Area Waterway System is more diverse both in abundance as well as biomass (i.e., energy flows) in the late 2010's than it was in the late 1980's. Although external factors related to wastewater treatment increased water quality and likely led to these assemblage-level changes breakpoint analysis did not allow verification of causal mechanisms.
The performance of regional governments under the results-based budgeting framework: A two-stage sectoral analysis
Authors: Charles Vincent , Diaz Juan , Aparicio Juan
Published: February 2022

The results-based budgeting (RBB) framework is a public management strategy in which economic resources are allocated to certain budget programs, oriented towards delivering specific products and results to the population. The present paper analyzes the regional governments’ efficiency in using their economic resources, under the RBB framework, with an application to the Peruvian context. To this end, we employ a data envelopment analysis (DEA) model with bootstrapping. In the first stage, different sectors of the regional governments are considered individually: education, security, health, sanitation, transportation, and recreation. In the second stage, the overall efficiency index is calculated using the sectoral indices obtained in the first stage. Finally, the factors or determinants influencing the level of efficiency are analyzed. The results show improvements in efficiency levels in the areas of health and sanitation, to the detriment of the rest of the sectors. The average overall efficiency level over the period 2013–2016 remains in the range of 0.25–0.30, which indicates an inefficiency level of 70%. Finally, the variables fiscal autonomy, capital stock, and population density show a positive relationship with respect to the overall efficiency index.
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

This 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

The 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.
Is There a Risk of Saddle Nose Deformity after Spreader Grafts and Flaps?
Authors: Eweiss Ahmed
Published: February 2022

Spreader grafts have been used successfully for years to augment the nasal valves among other indications. Spreader flaps have been described as an alternative. However, the literature discussing the complications of these procedures is scarce. This study aims to report and discuss the improvements and complications resulting from using spreader grafts or flaps in a cohort of patients operated upon by the author. Particular stress is given to a group of patients who developed saddle nose deformity after surgery. This cohort included 80 cases of rhinoplasty involving the use of spreader grafts or/and flaps. There was a highly significant improvement in nasal functions postoperatively. Postoperative saddle nose deformity was observed in five patients (6.25%). Spreader grafts/flaps are highly effective in improving nasal functions, but saddle nose deformity appears to be a possible risk. This complication has not been previously reported in the literature in relation to these procedures.
Predictive Value of Ki-67 Index in Evaluating Sporadic Vestibular Schwannoma Recurrence: Systematic Review and Meta-analysis
Authors: Vakharia Kunal , Hasegawa Hirotaka , Graffeo Christopher , Noureldine Mohammad H. A. , Cohen-Cohen Salomon , Perry Avital , Carlson Matthew L. , Driscoll Colin L. W. , Peris-Celda Maria , Van Gompel Jamie J. , Link Michael J.
Published: February 2022

Introduction Ki-67 is often used as a proliferation index to evaluate how aggressive a tumor is and its likelihood of recurrence. Vestibular schwannomas (VS) are a unique benign pathology that lends itself well to evaluation with Ki-67 as a potential marker for disease recurrence or progression following surgical resection.

Methods All English language studies of VSs and Ki-67 indices were screened. Studies were considered eligible for inclusion if they reported series of VSs undergoing primary resection without prior irradiation, with outcomes including both recurrence/progression and Ki-67 for individual patients. For published studies reporting pooled Ki-67 index data without detailed by-patient values, we contacted the authors to request data sharing for the current meta-analysis. Studies reporting a relationship between Ki-67 index and clinical outcomes in VS for which detailed patients' outcomes or Ki-67 indices could not be obtained were incorporated into the descriptive analysis, but excluded from the formal (i.e., quantitative) meta-analysis.

Results A systematic review identified 104 candidate citations of which 12 met inclusion criteria. Six of these studies had accessible patient-specific data. Individual patient data were collected from these studies for calculation of discrete study effect sizes, pooling via random-effects modeling with restricted maximum likelihood, and meta-analysis. The standardized mean difference in Ki-67 indices between those with and without recurrence was calculated as 0.79% (95% confidence interval [CI]: 0.28–1.30; p = 0.0026).

Conclusion Ki-67 index may be higher in VSs that demonstrate recurrence/progression following surgical resection. This may represent a promising means of evaluating tumor recurrence and potential need for early adjuvant therapy for VSs.