bluuebunny/crossref_metadata_2025 huggingface dataset:
Hsp70 in Redox Homeostasis
Authors: Zhang Hong , Gong Weibin , Wu Si , Perrett Sarah
Published: March 2022

Cellular redox homeostasis is precisely balanced by generation and elimination of reactive oxygen species (ROS). ROS are not only capable of causing oxidation of proteins, lipids and DNA to damage cells but can also act as signaling molecules to modulate transcription factors and epigenetic pathways that determine cell survival and death. Hsp70 proteins are central hubs for proteostasis and are important factors to ameliorate damage from different kinds of stress including oxidative stress. Hsp70 members often participate in different cellular signaling pathways via their clients and cochaperones. ROS can directly cause oxidative cysteine modifications of Hsp70 members to alter their structure and chaperone activity, resulting in changes in the interactions between Hsp70 and their clients or cochaperones, which can then transfer redox signals to Hsp70-related signaling pathways. On the other hand, ROS also activate some redox-related signaling pathways to indirectly modulate Hsp70 activity and expression. Post-translational modifications including phosphorylation together with elevated Hsp70 expression can expand the capacity of Hsp70 to deal with ROS-damaged proteins and support antioxidant enzymes. Knowledge about the response and role of Hsp70 in redox homeostasis will facilitate our understanding of the cellular knock-on effects of inhibitors targeting Hsp70 and the mechanisms of redox-related diseases and aging.
Synergistic Anti-Ageing through Senescent Cells Specific Reprogramming
Authors: Chen Rui , Skutella Thomas
Published: March 2022

In this review, we seek a novel strategy for establishing a rejuvenating microenvironment through senescent cells specific reprogramming. We suggest that partial reprogramming can produce a secretory phenotype that facilitates cellular rejuvenation. This strategy is desired for specific partial reprogramming under control to avoid tumour risk and organ failure due to loss of cellular identity. It also alleviates the chronic inflammatory state associated with ageing and secondary senescence in adjacent cells by improving the senescence-associated secretory phenotype. This manuscript also hopes to explore whether intervening in cellular senescence can improve ageing and promote damage repair, in general, to increase people’s healthy lifespan and reduce frailty. Feasible and safe clinical translational protocols are critical in rejuvenation by controlled reprogramming advances. This review discusses the limitations and controversies of these advances’ application (while organizing the manuscript according to potential clinical translation schemes) to explore directions and hypotheses that have translational value for subsequent research.
Combined TLR-3/TLR-8 Signaling in the Presence of α-Type-1 Cytokines Represents a Novel and Potent Dendritic Cell Type-1, Anti-Cancer Maturation Protocol
Authors: Fevžer Tadej , Poženel Primož , Zajc Kaja , Tešić Nataša , Švajger Urban
Published: March 2022

During the ex vivo generation of anti-cancer dendritic cell (DC)-based vaccines, their maturation still represents one of the most crucial steps of the manufacturing process. A superior DC vaccine should: possess extensive expression of co-stimulatory molecules, have an exceptional type-1 polarization capacity characterized by their ability to produce IL-12p70 upon contact with responding T cells, migrate efficiently toward chemokine receptor 7 (CCR7) ligands, and have a superior capacity to activate cytotoxic T cell responses. A major advance has been achieved with the discovery of the next generation maturation protocol involving TLR-3 agonist (poly I:C), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, interferon (IFN)-γ, and IFN-α, and has since been known as α-type-1 maturation cocktail. We demonstrate how this combination can be greatly enhanced by the inclusion of a TLR-8 stimulation (R848), thereby contributing to potentiation between different TLR signaling pathways. For maximum efficiency, TLR-3 stimulation should precede (termed pre I:C) the stimulation with the R848/TNF-α/IL-1β/IFN-α/IFN-γ cocktail. When compared to DCs matured with α-type-1 maturation cocktail (αDCs), DCs matured with pre I:C/R848/TNF-α/IL-1β/IFN-α/IFN-γ (termed zDCs) displayed higher expression of CD80 and CD86 co-stimulatory molecules. Importantly, after CD40-ligand stimulation, which simulates DC-T cell contact, zDCs were much more proficient in IL-12p70 production. In comparison to αDCs, zDCs also displayed a significantly greater migratory capacity toward chemokine ligands (CCL)19 and CCL21, and had a significantly greater allo-stimulatory capacity. Finally, zDCs were also superior in their capacity to induce melanoma-specific CD8+ T cells, CD8+ T cell proliferation, and cytotoxic T cells, which produced approximately two times more IFN-γ and more granzyme B, than those stimulated with αDCs. In conclusion, we present a novel and superior DC maturation cocktail that could be easily implemented into next generation DC vaccine manufacturing protocols in future trials.
MiR-30a-5p Alters Epidermal Terminal Differentiation during Aging by Regulating BNIP3L/NIX-Dependent Mitophagy
Authors: Chevalier Fabien P. , Rorteau Julie , Ferraro Sandra , Martin Lisa S. , Gonzalez-Torres Alejandro , Berthier Aurore , El Kholti Naima , Lamartine Jérôme
Published: March 2022

Chronological aging is characterized by an alteration in the genes’ regulatory network. In human skin, epidermal keratinocytes fail to differentiate properly with aging, leading to the weakening of the epidermal function. MiR-30a is particularly overexpressed with epidermal aging, but the downstream molecular mechanisms are still uncovered. The aim of this study was to decipher the effects of miR-30a overexpression in the human epidermis, with a focus on keratinocyte differentiation. We formally identified the mitophagy receptor BNIP3L as a direct target of miR-30a. Using a 3D organotypic model of reconstructed human epidermis overexpressing miR-30a, we observed a strong reduction in BNIP3L expression in the granular layer. In human epidermal sections of skin biopsies from donors of different ages, we observed a similar pattern of BNIP3L decreasing with aging. Moreover, human primary keratinocytes undergoing differentiation in vitro also showed a decreased expression of BNIP3L with age, together with a retention of mitochondria. Moreover, aging is associated with altered mitochondrial metabolism in primary keratinocytes, including decreased ATP-linked respiration. Thus, miR-30a is a negative regulator of programmed mitophagy during keratinocytes terminal differentiation, impairing epidermal homeostasis with aging.
Immunoproteasome Activity in Chronic Lymphocytic Leukemia as a Target of the Immunoproteasome-Selective Inhibitors
Authors: Besse Andrej , Kraus Marianne , Mendez-Lopez Max , Maurits Elmer , Overkleeft Herman S. , Driessen Christoph , Besse Lenka
Published: March 2022

Targeting proteasome with proteasome inhibitors (PIs) is an approved treatment strategy in multiple myeloma that has also been explored pre-clinically and clinically in other hematological malignancies. The approved PIs target both the constitutive and the immunoproteasome, the latter being present predominantly in cells of lymphoid origin. Therapeutic targeting of the immunoproteasome in cells with sole immunoproteasome activity may be selectively cytotoxic in malignant cells, while sparing the non-lymphoid tissues from the on-target PIs toxicity. Using activity-based probes to assess the proteasome activity profile and correlating it with the cytotoxicity assays, we identified B-cell chronic lymphocytic leukemia (B-CLL) to express predominantly immunoproteasome activity, which is associated with high sensitivity to approved proteasome inhibitors and, more importantly, to the immunoproteasome selective inhibitors LU005i and LU035i, targeting all immunoproteasome active subunits or only the immunoproteasome β5i, respectively. At the same time, LU102, a proteasome β2 inhibitor, sensitized B-CLL or immunoproteasome inhibitor-inherently resistant primary cells of acute myeloid leukemia, B-cell acute lymphoblastic leukemia, multiple myeloma and plasma cell leukemia to low doses of LU035i. The immunoproteasome thus represents a novel therapeutic target, which warrants further testing with clinical stage immunoproteasome inhibitors in monotherapy or in combinations.
A New Gal in Town: A Systematic Review of the Role of Galanin and Its Receptors in Experimental Pain
Authors: Fonseca-Rodrigues Diana , Almeida Armando , Pinto-Ribeiro Filipa
Published: March 2022

Galanin is a neuropeptide expressed in a small percentage of sensory neurons of the dorsal root ganglia and the superficial lamina of the dorsal horn of the spinal cord. In this work, we systematically reviewed the literature regarding the role of galanin and its receptors in nociception at the spinal and supraspinal levels, as well as in chronic pain conditions. The literature search was performed in PubMed, Web of Science, Scopus, ScienceDirect, OVID, TRIP, and EMBASE using “Galanin” AND “pain” as keywords. Of the 1379 papers that were retrieved in the initial search, we included a total of 141 papers in this review. Using the ARRIVE guidelines, we verified that 89.1% of the works were of good or moderate quality. Galanin shows a differential role in pain, depending on the pain state, site of action, and concentration. Under normal settings, galanin can modulate nociceptive processing through both a pro- and anti-nociceptive action, in a dose-dependent manner. This peptide also plays a key role in chronic pain conditions and its antinociceptive action at both a spinal and supraspinal level is enhanced, reducing animals’ hypersensitivity to both mechanical and thermal stimulation. Our results highlight galanin and its receptors as potential therapeutic targets in pain conditions.
Autologous Haematopoietic Stem Cell Transplantation and Systemic Sclerosis: Focus on Interstitial Lung Disease
Authors: Bagnato Gianluca , Versace Antonio Giovanni , La Rosa Daniela , De Gaetano Alberta , Imbalzano Egidio , Chiappalone Marianna , Ioppolo Carmelo , Roberts William Neal , Bitto Alessandra , Irrera Natasha , Allegra Alessandro , Pioggia Giovanni , Gangemi Sebastiano
Published: March 2022

Autologous hematopoietic stem cells transplantation (AHSCT) has been employed as treatment for severe systemic sclerosis (SSc) with high risk of organ failure. In the last 25 years overall survival and treatment-related mortality have improved, in accordance with a better patient selection and mobilization and conditioning protocols. This review analyzes the evidence from the last 5 years for AHSCT-treated SSc patients, considering in particular the outcomes related to interstitial lung disease. There are increasing data supporting the use of AHSCT in selected patients with rapidly progressive SSc. However, some unmet needs remain, such as an accurate patient selection, pre-transplantation analysis to identify subclinical conditions precluding the transplantation, and the alternatives for post-transplant ILD recurrence.
Regulating Endogenous Neural Stem Cell Activation to Promote Spinal Cord Injury Repair
Authors: Gilbert Emily A. B. , Lakshman Nishanth , Lau Kylie S. K. , Morshead Cindi M.
Published: March 2022

Spinal cord injury (SCI) affects millions of individuals worldwide. Currently, there is no cure, and treatment options to promote neural recovery are limited. An innovative approach to improve outcomes following SCI involves the recruitment of endogenous populations of neural stem cells (NSCs). NSCs can be isolated from the neuroaxis of the central nervous system (CNS), with brain and spinal cord populations sharing common characteristics (as well as regionally distinct phenotypes). Within the spinal cord, a number of NSC sub-populations have been identified which display unique protein expression profiles and proliferation kinetics. Collectively, the potential for NSCs to impact regenerative medicine strategies hinges on their cardinal properties, including self-renewal and multipotency (the ability to generate de novo neurons, astrocytes, and oligodendrocytes). Accordingly, endogenous NSCs could be harnessed to replace lost cells and promote structural repair following SCI. While studies exploring the efficacy of this approach continue to suggest its potential, many questions remain including those related to heterogeneity within the NSC pool, the interaction of NSCs with their environment, and the identification of factors that can enhance their response. We discuss the current state of knowledge regarding populations of endogenous spinal cord NSCs, their niche, and the factors that regulate their behavior. In an attempt to move towards the goal of enhancing neural repair, we highlight approaches that promote NSC activation following injury including the modulation of the microenvironment and parenchymal cells, pharmaceuticals, and applied electrical stimulation.
Severe COVID-19 Shares a Common Neutrophil Activation Signature with Other Acute Inflammatory States
Authors: Schimke Lena F. , Marques Alexandre H. C. , Baiocchi Gabriela Crispim , de Souza Prado Caroline Aliane , Fonseca Dennyson Leandro M. , Freire Paula Paccielli , Rodrigues Plaça Desirée , Salerno Filgueiras Igor , Coelho Salgado Ranieri , Jansen-Marques Gabriel , Rocha Oliveira Antonio Edson , Peron Jean Pierre Schatzmann , Cabral-Miranda Gustavo , Barbuto José Alexandre Marzagão , Camara Niels Olsen Saraiva , Calich Vera Lúcia Garcia , Ochs Hans D. , Condino-Neto Antonio , Overmyer Katherine A. , Coon Joshua J. , Balnis Joseph , Jaitovich Ariel , Schulte-Schrepping Jonas , Ulas Thomas , Schultze Joachim L. , Nakaya Helder I. , Jurisica Igor , Cabral-Marques Otávio
Published: March 2022

Severe COVID-19 patients present a clinical and laboratory overlap with other hyperinflammatory conditions such as hemophagocytic lymphohistiocytosis (HLH). However, the underlying mechanisms of these conditions remain to be explored. Here, we investigated the transcriptome of 1596 individuals, including patients with COVID-19 in comparison to healthy controls, other acute inflammatory states (HLH, multisystem inflammatory syndrome in children [MIS-C], Kawasaki disease [KD]), and different respiratory infections (seasonal coronavirus, influenza, bacterial pneumonia). We observed that COVID-19 and HLH share immunological pathways (cytokine/chemokine signaling and neutrophil-mediated immune responses), including gene signatures that stratify COVID-19 patients admitted to the intensive care unit (ICU) and COVID-19_nonICU patients. Of note, among the common differentially expressed genes (DEG), there is a cluster of neutrophil-associated genes that reflects a generalized hyperinflammatory state since it is also dysregulated in patients with KD and bacterial pneumonia. These genes are dysregulated at the protein level across several COVID-19 studies and form an interconnected network with differentially expressed plasma proteins that point to neutrophil hyperactivation in COVID-19 patients admitted to the intensive care unit. scRNAseq analysis indicated that these genes are specifically upregulated across different leukocyte populations, including lymphocyte subsets and immature neutrophils. Artificial intelligence modeling confirmed the strong association of these genes with COVID-19 severity. Thus, our work indicates putative therapeutic pathways for intervention.
MicroRNA-1270 Inhibits Cell Proliferation, Migration, and Invasion via Targeting IRF8 in Osteoblast-like Cell Lines
Authors: Ramírez-Salazar Eric Gustavo , Almeraya Erika Victoria , López-Perez Tania Valentina , Jiménez-Salas Zacarías , Patiño Nelly , Velázquez-Cruz Rafael
Published: March 2022

Osteoporosis (OP) is the most common bone disease affecting elderly individuals. The diagnosis of this pathology is most commonly made on the basis of bone fractures. Several microRNAs (miRNAs/miRs) have been identified as possible biomarkers for the diagnosis and treatment of OP. miRNAs can regulate gene expression, and determining their functions can provide potential pharmacological targets for treating OP. A previous study showed that miR-1270 was upregulated in monocytes derived from postmenopausal women with OP. Therefore, the present study aimed to uncover the role of miR-1270 in regulating bone metabolism. To reveal the mechanism underlying the regulatory effect of miR-1270 on interferon regulatory factor 8 (IRF8) expression, luciferase assay, reverse transcription-quantitative PCR, and Western blot analysis were performed. The results suggest that miR-1270 could regulate the mRNA and protein expression levels of IRF8 by directly binding to its 3′-untranslated region. The effects of miR-1270 overexpression and IRF8 silencing on cell proliferation, migration, and invasion were also evaluated. To the best of our knowledge, the current study was the first to support the crucial role of miR-1270 in bone metabolism via modulation of IRF8 expression. In addition, miR-1270 overexpression could attenuate human osteoblast-like cells’ proliferation and migration ability.
Alternate Causes for Pathogenesis of Exfoliation Glaucoma, a Multifactorial Elastotic Disorder: A Literature Review
Authors: Chakraborty Munmun , Rao Aparna
Published: March 2022

Exfoliation glaucoma (XFG) is the most recognizable form of secondary open-angle glaucoma associated with a high risk of blindness. This disease is characterized by white flaky granular deposits in the anterior chamber that leads to the elevation of intraocular pressure (IOP) and subsequent glaucomatous optic nerve damage. Conventionally, XFG is known to respond poorly to medical therapy, and surgical intervention is the only management option in most cases. Various genetic and nongenetic factors are known to be linked to the development of XFG. Despite decades of research on the genetic factors in exfoliation syndrome (XFS) by study groups and global consortia involving different ethnic populations, the pathogenesis of XFS and the mechanism of onset of glaucoma still remains an unsolved mystery. The key lies in understanding how the function of a gene (or set of genes) is altered by environmental triggers, along with other molecular events that underlie the key disease attributes, namely, oxidative stress and the disruption of the blood–aqueous barrier (BAB). It remains a challenge to evolve a theory encompassing all factions of molecular events occurring independently or parallelly that determine the disease manifestation (phenotype) or the stage of the disease in the eye (or in any tissue) in exfoliation. Our enhanced understanding of the underlying molecular pathophysiology of XFG, beyond the known genes or polymorphisms involved in the disease, will lead to improved diagnosis and management and the ability to recognize how the environment influences these key events that lead to the disease phenotype or disease progression. This review summarizes the recent observations and discoveries of four key factors that may hold the answers to the non-lysyl oxidase-like 1 (LOXL1) mechanisms behind XFG pathogenesis, namely, the epigenetic factor miRNA, disordered autophagy along with the potential involvement of mitochondrial mutations, and a compromised aqueous–blood barrier.
Immunohistochemical Evaluation of CD3, CD4, CD8, and CD20 in Decidual and Trophoblastic Tissue Specimens of Patients with Recurrent Pregnancy Loss
Authors: Kavvadas Dimitrios , Karachrysafi Sofia , Anastasiadou Pinelopi , Kavvada Asimoula , Fotiadou Stella , Papachristodoulou Angeliki , Papamitsou Theodora , Sioga Antonia
Published: March 2022

Recurrent miscarriages affect up to 5% of couples. CD3+ (T-lymphocytes), CD4+ (helper T-lymphocytes), CD8+ (cytotoxic T-lymphocytes), and CD20+ (B-lymphocytes) cells may participate in the pathophysiology of recurrent pregnancy loss (RPL). The aim of this study was to investigate the complicity of these molecules in RPL. The experimental specimens were obtained from 20 females who underwent miscarriages in the first gestational trimester, while the control group’s specimens consisted of 20 females who proceeded with voluntary pregnancy termination during the same period. Tissue samples were taken from the decidua basalis, decidua parietalis, and trophoblast (placental chorionic villi) and were studied using immunohistochemical methods. Monoclonal antibodies were used against CD3, CD4, CD8, and CD20 cells. The lymphocyte levels in the decidua parietalis displayed profound disparities among the two groups. The decidua basalis and trophoblast exhibited almost the same disparities regarding positive CD cells. The comparison of CD4+ and CD8+ cells in the endometrial tissue revealed a significant difference between the two groups of study. The analysis uncovered a strong relationship between RPL and the presence of CD3+, CD4+, CD8+, and CD20+ cells in the decidua parietalis tissue. The number of positive T cells was decreased in the decidual basalis and chorionic villi, proving that their absence significantly disrupts the balance of the immunological environment.
Investigation on the Painting Materials and Profile Structures Used in Ancient Chinese Folk Architectural Paintings by Multiple Analytical Methods
Authors: Zou Weihan , Yeo Sok-Yee
Published: March 2022

In order to understand the painting materials and profile structures used in the creation of Chinese ancient folk architectural paintings, the architectural paintings of the Bell and Drum Tower at Fushan Temple in Shaanxi Province of China was investigated. In this study, optical microscopy, Fourier transform infrared spectroscopy (FTIR), micro-Raman spectroscopy, scanning electron microscopy-energy-dispersive X-ray spectroscopy (SEM-EDS), and chemical experimental methods were used. The profile structures, and the elemental and chemical compositions of the pigments and binders in the ground layer of the 12 samples were determined. Results showed that the painting profile structures in both towers comprised of pigment layer, underpainting layer and ground layer, where no starch was found in the chalk ground layer. The pigment layer mainly comprised of iron oxide red, chalk, lapis lazuli, carbon black, green earth, and a dark green pigment that is formed by a combination of carbon black and green earth. To-date, the use of green earth pigment in Chinese architectural paintings was not found in Chinese related academic literature; hence, this study marked the first identification of green earth being used in the architectural paintings. Tung oil, commonly used in Chinese architectural paintings as a binder for pigment, was also identified in the samples. Results from this study will serve as an important reference for better scientific investigation methods on ancient Chinese folk painting materials.
YSZ/LSM Composite Cathode Deposited by Solution Precursor Plasma Spraying
Authors: Wang Xiaoming , Tang Boen , Wen Penghui , Dong Weiping , Wang Linlin , Wang Dongyun
Published: March 2022

In this paper, solution precursor plasma spraying (SPPS) was employed to prepare a porous YSZ/LSM composite cathode for solid oxide fuel cell (SOFC). The surface morphology and microstructure of the composite cathode deposits were characterized using SEM. The effect of annealing treatment on SPPS YSZ/LSM microstructure was examined. The results showed that the as-sprayed YSZ/LSM deposits presented a porous aggregate with a size range of 10–60 μm when the alcohol was used as the solvent and the spraying distance was 60 mm. The porous aggregate was found to be composed mainly of small particles ranging from 0.2–2 μm, the YSZ/LSM composite cathode showed a finely porous microstructure with grain sizes from micrometers to sub-micrometers. A further annealing treatment at 1050 °C for 2 h in air resulted in a continuous microstructure porous coating with a perovskite phase. The polarization test results demonstrated that the minimum polarizations were 1.26 and 0.083 Ω·cm2 for the composite cathode at 800 and 1000 °C, respectively.
Response of Phytoplankton Community Structure to Vegetation Restoration after Removal of Purse Seine in Shengjin Lake
Authors: Zheng Xudong , Chen Jingwen , Guo Wenli , Zhou Zhongze , Ye Xiaoxin
Published: March 2022

Aquatic vegetation has been restored since the removal of seine nets from the lake surface of Shengjin Lake in 2018. Through four seasons of phytoplankton sampling surveys from 2019–2020, we analyzed spatial and temporal changes in phytoplankton communities, water quality, and aquatic plant recovery in conjunction with previous research literature to reveal the response mechanisms of phytoplankton community structure to rapidly recovering aquatic vegetation. The results showed that the Secchi depth increased (0.4 m to 0.7 m), the concentration of total phosphorus decreased (0.053 mg/L to 0.41 mg/L), the species of aquatic plants (5 species to 16 species), phytoplankton species (210 species to 254 species) and cell density increased after the removal of the seine. Since the removal of the seine of Shengjin Lake, the aquatic vegetation cover has exceeded 80%, the phytoplankton biodiversity has increased, and the water quality has recovered to II-III water status. Our results show that aquatic plants improve water quality through direct and indirect effects and influence phytoplankton community structure together with the water environment, which can provide guidance for the restoration situation of the middle and lower reaches of the Yangtze River through-river lake ecosystems.
Global Medicinal Use of Bats: A Systematic Literature and Social Media Review
Authors: Tackett Elaine S. , Kingston Tigga , Sadeghmoghaddam Narges , Rutrough Abigail L.
Published: March 2022

The hunting of bats for food and medicine is one of the greatest threats to bat conservation. While hunting for consumption is the focus of increased attention, the specific medicinal uses of bats are poorly documented, limiting mitigation efforts. Here, we determine the distribution of bat hunting for food and medicinal use and characterize medicinal use practices. We systematically surveyed English-language scientific literature and social media platforms utilizing keywords and hashtags in 27 languages. We found 198 papers and 1063 social media posts from 83 countries and territories. Although use for food was more common, with 1284 unique reports from 71 countries, bats were used to treat 42 ailments of 11 human body systems across 37 countries (453 reports). Asthma was the most common ailment, distantly followed by kidney conditions. Ten organs or body parts of bats were used medicinally, with bat meat (flesh) and fluids (blood, bile, and oil) the most common. Understanding the effects and drivers of specific bat hunting practices will help guide conservation and public health efforts in the communities where bats are hunted. By pinpointing the ailments bats are being used for, outreach and alternative treatments can be introduced to replace the use of bats.
Fatty Acid Composition of Dairy Milk: A Case Study Comparing Once- and Twice-a-Day Milking of Pasture-Fed Cows at Different Stages of Lactation
Authors: Sanjayaranj Inthujaa , Lopez-Villalobos Nicolas , Blair Hugh , Janssen Patrick , Holroyd Stephen , MacGibbon Alastair
Published: March 2022

In this case study, we compared the gross composition and fatty acid (FA) composition of milk from cows milked once a day (OAD) and twice a day (TAD) at different stages of lactation in real farm conditions with no control on feed. Seventy-two cows from a OAD milking herd and 181 cows from a TAD milking herd were sampled in early, mid and late lactation. Calibration equations were developed to enable the prediction of proportions of individual FAs using mid-infrared (MIR) spectroscopy. Cows milked OAD produced 25% lower daily milk yield (MY) compared to cows milked TAD. Percentages of fat and protein were 21% and 9% higher in cows milked OAD compared to cows milked TAD, respectively. The proportion of saturated fatty acids (SFA) (molecules with unbranched hydrocarbon chains and all single bonds) was significantly lower, while the proportions of de novo synthesised FAs from C8:0 to C14:0 were significantly higher, in cows milked OAD compared to cows milked TAD. OAD milking improved the energy balance of cows, which led to higher proportions of de novo synthesised FAs and lower proportions of long-chain fatty acids (16:0 and above). The proportion of SFA was significantly higher in mid lactation (ML) compared to early lactation (EL) and late lactation (LL) in cows milked OAD and TAD. In EL, the proportions of C4:0 to C12:0 FAs in cows milked OAD were significantly higher compared to the cows milked TAD due to the improved energy status of cows milked OAD. Understanding the proportions of individual FAs in cows milked OAD and TAD will enable further studies on milk fat characteristics and on butter hardness and coagulation properties of milk.
Post-Acquisition Hyperpolarized 29Silicon Magnetic Resonance Image Processing for Visualization of Colorectal Lesions Using a User-Friendly Graphical Interface
Authors: McCowan Caitlin V. , Salmon Duncan , Hu Jingzhe , Pudakalakatti Shivanand , Whiting Nicholas , Davis Jennifer S. , Carson Daniel D. , Zacharias Niki M. , Bhattacharya Pratip K. , Farach-Carson Mary C.
Published: March 2022

Medical imaging devices often use automated processing that creates and displays a self-normalized image. When improperly executed, normalization can misrepresent information or result in an inaccurate analysis. In the case of diagnostic imaging, a false positive in the absence of disease, or a negative finding when disease is present, can produce a detrimental experience for the patient and diminish their health prospects and prognosis. In many clinical settings, a medical technical specialist is trained to operate an imaging device without sufficient background information or understanding of the fundamental theory and processes involved in image creation and signal processing. Here, we describe a user-friendly image processing algorithm that mitigates user bias and allows for true signal to be distinguished from background. For proof-of-principle, we used antibody-targeted molecular imaging of colorectal cancer (CRC) in a mouse model, expressing human MUC1 at tumor sites. Lesion detection was performed using targeted magnetic resonance imaging (MRI) of hyperpolarized silicon particles. Resulting images containing high background and artifacts were then subjected to individualized image post-processing and comparative analysis. Post-acquisition image processing allowed for co-registration of the targeted silicon signal with the anatomical proton magnetic resonance (MR) image. This new methodology allows users to calibrate a set of images, acquired with MRI, and reliably locate CRC tumors in the lower gastrointestinal tract of living mice. The method is expected to be generally useful for distinguishing true signal from background for other cancer types, improving the reliability of diagnostic MRI.
Olfactory Neuroblastoma: Re-Evaluating the Paradigm of Intracranial Extension and Cyst Formation
Authors: Dumont Rebecca A. , Palma Diaz Miguel Fernando , Hsu William , Sepahdari Ali R.
Published: March 2022

The purpose of the current study was to assess the prevalence of cyst formation at the brain-tumor interface in olfactory neuroblastoma. We used the UCLA patient-based Pathology and Radiology Head and Neck Database (UPP&R HAND) to identify the largest patient cohort reported to date with imaging and pathology data. Eighteen of thirty-one patients (58.1%) had evidence of intracranial extension on MRI, while four (22.0%) demonstrated cyst formation at the brain–tumor interface. The extent of intracranial extension was by far the strongest predictor for intracranial cyst formation, regardless of Hyams tumor grade, using a binary logistics regression model (p = 0.002) and ROC curve analysis (AUC 94.6%). Cyst formation at the brain-tumor interface was an uncommon imaging finding, and tends to occur with a larger component of intracranial tumor extension.
DNN Intellectual Property Extraction Using Composite Data
Authors: Mosafi Itay , David Eli (Omid) , Altshuler Yaniv , Netanyahu Nathan S.
Published: March 2022

As state-of-the-art deep neural networks are being deployed at the core level of increasingly large numbers of AI-based products and services, the incentive for “copying them” (i.e., their intellectual property, manifested through the knowledge that is encapsulated in them) either by adversaries or commercial competitors is expected to considerably increase over time. The most efficient way to extract or steal knowledge from such networks is by querying them using a large dataset of random samples and recording their output, which is followed by the training of a student network, aiming to eventually mimic these outputs, without making any assumption about the original networks. The most effective way to protect against such a mimicking attack is to answer queries with the classification result only, omitting confidence values associated with the softmax layer. In this paper, we present a novel method for generating composite images for attacking a mentor neural network using a student model. Our method assumes no information regarding the mentor’s training dataset, architecture, or weights. Furthermore, assuming no information regarding the mentor’s softmax output values, our method successfully mimics the given neural network and is capable of stealing large portions (and sometimes all) of its encapsulated knowledge. Our student model achieved 99% relative accuracy to the protected mentor model on the Cifar-10 test set. In addition, we demonstrate that our student network (which copies the mentor) is impervious to watermarking protection methods and thus would evade being detected as a stolen model by existing dedicated techniques. Our results imply that all current neural networks are vulnerable to mimicking attacks, even if they do not divulge anything but the most basic required output, and that the student model that mimics them cannot be easily detected using currently available techniques.
Ungulate Detection and Species Classification from Camera Trap Images Using RetinaNet and Faster R-CNN
Authors: Vecvanags Alekss , Aktas Kadir , Pavlovs Ilja , Avots Egils , Filipovs Jevgenijs , Brauns Agris , Done Gundega , Jakovels Dainis , Anbarjafari Gholamreza
Published: March 2022

Changes in the ungulate population density in the wild has impacts on both the wildlife and human society. In order to control the ungulate population movement, monitoring systems such as camera trap networks have been implemented in a non-invasive setup. However, such systems produce a large number of images as the output, hence making it very resource consuming to manually detect the animals. In this paper, we present a new dataset of wild ungulates which was collected in Latvia. Moreover, we demonstrate two methods, which use RetinaNet and Faster R-CNN as backbones, respectively, to detect the animals in the images. We discuss the optimization of training and impact of data augmentation on the performance. Finally, we show the result of aforementioned tune networks over the real world data collected in Latvia.
From Micro to Macro: A Relativistic Treatment of the Chiral Energy Shifts Caused by Static Electromagnetic Effects on Free Electrons
Authors: Kurian Philip
Published: March 2022

Free electron systems are ubiquitous in nature and have demonstrated intriguing effects in their collective interactions with weak electric and magnetic fields, especially in aqueous environments. Starting from the Dirac Hamiltonian, a fully relativistic expression is derived for the electron energy shift in the presence of a spatiotemporally constant, weak electromagnetic field. The expectation value of this energy shift is then computed explicitly using the Fourier transforms of the fermionic fields. To first order in the electromagnetic fields, the average relativistic energy shift is found to be completely independent of the electron spin-polarization coefficients. This effect is also considerably larger than that predicted in quantum mechanics by the analogous Zeeman shift. Finally, in the non-relativistic limit, it is shown how to discriminate between achiral and completely polarized states, which leads to a concluding discussion of possible mesoscopic and macroscopic manifestations of electron spin states across many orders of magnitude in the physical world, with stark implications for biological and other complex systems.
Educational Psychologists as ‘Dissenting Voices’: Thinking Again about Educational Psychologists and Social Justice
Authors: Mercieca Daniela , Mercieca Duncan P.
Published: March 2022

This paper locates the educational psychologist’s (EP) involvement in addressing social justice in practice. It uses some philosophical ideas from Jacques Rancière, particularly the idea of the distribution of the sensible and dissensus, to help us question how systems that are aimed at contributing to a socially just society can limit social justice itself. Whilst the argument of this paper is applicable to educational psychologists internationally, this paper is situated within a Scottish context. It uses a vignette to draw out a philosophical reading of the EP’s involvement in the narrative. This paper gives some examples of how structures that are aimed at supporting social justice often position the EPs within these systems so that thinking, being and doing are shaped according to the structures that they inhabit. The establishment of such structures and discourses have limited the meaning and implementation of social justice. This means that the identity of both those requiring the involvement of the EP, as well as the EP and other professionals is determined in terms of their ‘proper place’ and their activity is determined in terms of its ‘proper function’. The paper argues that EPs can interrupt the procedural flow and provide a dissenting voice which can ultimately lead to social justice in ways that the normal flow of procedure does not.
Distributed Online Risk Assessment in the National Cyberspace
Authors: Karbowski Andrzej
Published: March 2022

The paper presents a distributed approach to online cyber risk assessment across the country, taking into account cyber threats and vulnerabilities identified by local services operators. It consists in distributed, asynchronous calculations of possible failure scenarios. They are a solution of a set of nonlinear, nonsmooth equations with locally assessed risk activation functions as inputs. These functions indicate whether a given threat is expected in some future period. The convergence condition of the mentioned algorithm is given in the theorem form. At the end, a case study concerning a system consisting of four entities is presented.
An Intelligent System to Detect Advanced Persistent Threats in Industrial Internet of Things (I-IoT)
Authors: Javed Safdar Hussain , Ahmad Maaz Bin , Asif Muhammad , Almotiri Sultan H. , Masood Khalid , Ghamdi Mohammad A. Al
Published: March 2022

The Industrial Internet of Things (I-IoT) is a manifestation of an extensive industrial network that interconnects various sensors and wireless devices to integrate cyber and physical systems. While I-IoT provides a considerable advantage to large-scale industrial enterprises, it is prone to significant security challenges in the form of sophisticated attacks such as Advanced Persistent Threat (APT). APT is a serious security challenge to all kinds of networks, including I-IoT. It is a stealthy threat actor, characteristically a nation-state or state-sponsored group that launches a cyber attack intending to gain unauthorized access to a computer network and remain undetected for a longer period. The latest intrusion detection systems face several challenges in detecting such complex cyber attacks in multifarious networks of I-IoT, where unpredictable and unexpected cyber attacks of such sophistication can lead to catastrophic effects. Therefore, these attacks need to be accurately and promptly detected in I-IoT. This paper presents an intelligent APT detection and classification system to secure I-IoT. After pre-processing, several machine learning algorithms are applied to detect and classify complex APT signatures accurately. The algorithms include Decision Tree, Random Forest, Support Vector Machine, Logistic Regression, Gaussian Naive Bayes, Bagging, Extreme Gradient Boosting and Adaboost, which are applied on a publicly available dataset KDDCup99. Moreover, a comparative analysis is conducted among ML algorithms to select the appropriate one for the targeted domain. The experimental results indicate that the Adaboost classifier outperforms the others with 99.9% accuracy with 0.012 s execution time for detecting APT attacks. Furthermore, results are compared with state-of-the-art techniques that depict the superiority of the proposed system. This system can be deployed in mission-critical scenarios in the I-IoT domain.
Parameter Sensitivity Analysis of a Brake Pressure Control System in Aviation Using an Electro-Hydraulic Servo Valve
Authors: He Xiaolong , Wang Yuan , Shi Yapeng , Du Chenhao , Yu Bin , Zhang Qiwei , Xie Zuojian , Xie Yan , Hou Xuekun
Published: March 2022

The landing gear system has the task of bearing the weight of the aircraft, bearing the impact load, and providing the braking function in the process of the aircraft taxiing, take-off, and landing. There are many parameters in the aviation brake pressure servo valve-controlled cylinder system (ABPSVCS) which will have a significant influence on the dynamic behavior of the system. Sensitivity analysis is an effective method to analyze the influence of system parameters on system characteristics, especially for nonlinear systems. The trajectory sensitivity method based on the description of system state space is used for the parameter sensitivity analysis of the ABPSVCS. By grouping various parameters for sensitivity analysis, the law of parameter sensitivity of each group is obtained, and the results are verified by experiments. The results can lay a theoretical and experimental foundation for the related research work of the aviation brake pressure servo valve.
Research on Performance Metrics and Environmental Conditions for 5G MIMO OTA
Authors: Qu Meijun , Chen Zihan , Liu Xianhui , Sun Siyang
Published: March 2022

For Multiple-input, multiple-output (MIMO) user equipment (UE), over-the-air (OTA) testing of radiated multi-antenna reception performance is crucial to guarantee actual network performance and is mandatory in North America, Europe and China. For 5G MIMO OTA, 3GPP has specified the clustered delay line (CDL) channel models as the reference channel models, which present higher order and directivity than those of 4G. Therefore, which kinds of performance metrics and environmental conditions are feasible and necessary to better characterize the MIMO performance should be studied. In this paper, MIMO OTA measurement results of different figures of merits (FoMs) under both UE noise-limited and interference-limited environmental conditions have been compared and discussed, respectively. In addition, the impact of different channel models on MIMO OTA throughput performance as well as the variance per azimuth are compared. Based on the analysis, Peak-Null can better reflect the difference between the 12 azimuth positions than Variance. Total Radiated Multi-antenna Sensitivity (TRMS) under both channel models presents nearly the same performance trends at different thresholds. On the contrary, MIMO Average Radiated SIR Sensitivity (MARSS) exhibits a high dependence on channel models. The MARSS under UMi channel model shows a much smaller performance variation between UEs than UMa channel model. TRMS under 3GPP UE noise-limited environmental condition exhibits a stronger ability to distinguish between good and bad performing devices than that of MARSS under CTIA interference-limited environmental condition. The discrepancy can reach 4 dB at most. This discrepancy does not come from different average manners between TRMS and MARSS, but originates from environmental condition itself. Therefore, it is proposed to adopt TRMS under UE noise-limited environmental condition as the unique or baseline test condition in 5G FR1 MIMO OTA. Peak-Null can be considered as a secondary FoM to characterize the variance per azimuth.
A Calibration-Free, 16-Channel, 50-MS/s, 14-Bit, Pipelined-SAR ADC with Reference/Op-Amp Sharing and Optimized Stage Resolution Distribution
Authors: Wu Yimin , Ye Fan , Ren Junyan
Published: March 2022

This paper presents a calibration-free, 16-channel, 14-bit, 50-MS/s, pipelined successive approximation register (pipelined-SAR) analog-to-digital converter (ADC) for ultrasound imaging systems. A reference sharing scheme with reduced buffers is proposed to improve area-and-power efficiency, which is essential for multi-channel systems. Based on this, a three-stage, pipelined-SAR ADC architecture with reference/op-amp sharing and optimized stage resolution distribution is proposed. The prototype ADC is designed in a 0.18-μm process with peripheral circuits integrated, including low-voltage differential signaling (LVDS), bandgap, etc. It achieves a robust and calibration-free performance with 68.25-dB signal to noise and distortion ratio (SNDR) and 82.19-dB spurious-free dynamic range (SFDR), translating into a competitive figure of merit (FoM) of 0.47 pJ/conversion-step among other high-resolution ADCs used in ultrasound applications.
A Wideband Reconfigurable CMOS VGA Based on an Asymmetric Capacitor Technique with a Low Phase Variation
Authors: Zhang Qingfeng , Zhao Chenxi , Kang Kai
Published: March 2022

This paper presents a wideband digitally controlled variable gain amplifier (VGA) with a reconfigurable gain tuning range and gain step in a 65 nm CMOS process. A unique asymmetric capacitor-based reconfigurable technique is proposed to extend the gain tuning range and realize gain step reconfiguration. An active neutralization topology based on a stackless transistor is utilized to compensate for the additional phase shift introduced by the gain tuning. Moreover, a current-type digital-to-analog converter (DAC) is also integrated for easier precise gain control. With the asymmetric capacitor varying from 1000 fF to 200 fF with a step of 400 fF, the proposed VGA achieves a 12.2/9.2/6.1 dB gain tuning range with a 0.4/0.3/0.2 dB gain resolution, respectively. At the maximum gain tuning range mode, the measured minimum root-mean-square (RMS) phase error is 1.7° at 23.4 GHz. At the finest gain step control mode, the RMS phase error measured across 20–30 GHz is lower than 1.9°. The tested result also shows the proposed VGA achieves a peak gain of 13 dB with a 3 dB bandwidth of 21.4–29 GHz, and the output 1 dB compression point (OP1dB) is up to 8.6 dBm at 25 GHz.