bluuebunny/crossref_metadata_2025 huggingface dataset:
Bispecific antibodies targeting CD40 and tumor-associated antigens promote cross-priming of T cells resulting in an antitumor response superior to monospecific antibodies
Authors: Hägerbrand Karin , Varas Laura , Deronic Adnan , Nyesiga Barnabas , Sundstedt Anette , Ljung Lill , Sakellariou Christina , Werchau Doreen , Thagesson Mia , Gomez Jimenez David , Greiff Lennart , Celander Mona , Smedenfors Kristine , Rosén Anna , Bölükbas Deniz , Carlsson Fredrika , Levin Mattias , Säll Anna , von Schantz Laura , Lindstedt Malin , Ellmark Peter
Published: November 2022

Background

Indications with poor T-cell infiltration or deficiencies in T-cell priming and associated unresponsiveness to established immunotherapies represent an unmet medical need in oncology. CD40-targeting therapies designed to enhance antigen presentation, generate new tumor-specific T cells, and activate tumor-infiltrating myeloid cells to remodel the tumor microenvironment, represent a promising opportunity to meet this need. In this study, we present the first in vivo data supporting a role for tumor-associated antigen (TAA)-mediated uptake and cross-presentation of tumor antigens to enhance tumor-specific T-cell priming using CD40×TAA bispecific antibodies, a concept we named Neo-X-Prime.

Methods

Bispecific antibodies targeting CD40 and either of two cell-surface expressed TAA, carcinoembryonic antigen-related cell adhesion molecule 5 (CEA) or epithelial cell adhesion molecule (EpCAM), were developed in a tetravalent format. TAA-conditional CD40 agonism, activation of tumor-infiltrating immune cells, antitumor efficacy and the role of delivery of tumor-derived material such as extracellular vesicles, tumor debris and exosomes by the CD40×TAA bispecific antibodies were demonstrated in vitro using primary human and murine cells and in vivo using human CD40 transgenic mice with different tumor models.

Results

The results showed that the CD40×TAA bispecific antibodies induced TAA-conditional CD40 activation both in vitro and in vivo. Further, it was demonstrated in vitro that they induced clustering of tumor debris and CD40-expressing cells in a dose-dependent manner and superior T-cell priming when added to dendritic cells (DC), ovalbumin (OVA)-specific T cells and OVA-containing tumor debris or exosomes. The antitumor activity of the Neo-X-Prime bispecific antibodies was demonstrated to be significantly superior to the monospecific CD40 antibody, and the resulting T-cell dependent antitumor immunity was directed to tumor antigens other than the TAA used for targeting (EpCAM).

Conclusions

The data presented herein support the hypothesis that CD40×TAA bispecific antibodies can engage tumor-derived vesicles containing tumor neoantigens to myeloid cells such as DCs resulting in an improved DC-mediated cross-priming of tumor-specific CD8+T cells. Thus, this principle may offer therapeutics strategies to enhance tumor-specific T-cell immunity and associated clinical benefit in indications characterized by poor T-cell infiltration or deficiencies in T-cell priming.
Both APRIL and antibody-fragment-based CAR T cells for myeloma induce BCMA downmodulation by trogocytosis and internalization
Authors: Camviel Nicolas , Wolf Benita , Croce Giancarlo , Gfeller David , Zoete Vincent , Arber Caroline
Published: November 2022

Background

Chimeric antigen receptor (CAR) T cell therapy targeting B cell maturation antigen (BCMA) on multiple myeloma (MM) produces fast but not long-lasting responses. Reasons for treatment failure are poorly understood. CARs simultaneously targeting two antigens may represent an alternative. Here, we (1) designed and characterized novel A proliferation inducing ligand (APRIL) based dual-antigen targeting CARs, and (2) investigated mechanisms of resistance to CAR T cells with three different BCMA-binding moieties (APRIL, single-chain-variable-fragment, heavy-chain-only).

Methods

Three new APRIL-CARs were designed and characterized. Human APRIL-CAR T cells were evaluated for their cytotoxic function in vitro and in vivo, for their polyfunctionality, immune synapse formation, memory, exhaustion phenotype and tonic signaling activity. To investigate resistance mechanisms, we analyzed BCMA levels and cellular localization and quantified CAR T cell–target cell interactions by live microscopy. Impact on pathway activation and tumor cell proliferation was assessed in vitro and in vivo.

Results

APRIL-CAR T cells in a trimeric ligand binding conformation conferred fast but not sustained antitumor responses in vivo in mouse xenograft models. In vitro trimer-BBζ CAR T cells were more polyfunctional and formed stronger immune synapses than monomer-BBζ CAR T cells. After CAR T cell–myeloma cell contact, BCMA was rapidly downmodulated on target cells with all evaluated binding moieties. CAR T cells acquired BCMA by trogocytosis, and BCMA on MM cells was rapidly internalized. Since BCMA can be re-expressed during progression and persisting CAR T cells may not protect patients from relapse, we investigated whether non-functional CAR T cells play a role in tumor progression. While CAR T cell–MM cell interactions activated BCMA pathway, we did not find enhanced tumor growth in vitro or in vivo.

Conclusion

Antitumor responses with APRIL-CAR T cells were fast but not sustained. Rapid BCMA downmodulation occurred independently of whether an APRIL or antibody-based binding moiety was used. BCMA internalization mostly contributed to this effect, but trogocytosis by CAR T cells was also observed. Our study sheds light on the mechanisms underlying CAR T cell failure in MM when targeting BCMA and can inform the development of improved treatment strategies.
Body composition of extreme performers in the US Marine Corps
Authors: Potter Adam W , Soto L D , Friedl K E
Published: November 2022

Background

The creation of highly muscled and strong fighters is a recurring theme in human performance enhancement concepts. Physical readiness standards, intended to prevent obesity in the military, produce contradictory objectives, hounding large individuals to lose weight because of confusion between body size and body composition. Through selection, specialised training and policy exceptions the US Marine Corps has successfully developed a unique group of large (body mass index (BMI) >30 kg/m2) and strong individuals, the body bearers (BB) who carry coffins of Marines to their final resting place.

Methods

We examined the relationship between adiposity and body size from nine male BB (age 25.0±2.1, height: 1.84±0.04 (1.80–1.92) m, BMI: 33.0±2.1 (30–37) kg/m2). Body composition was assessed by dual-energy X-ray absorptiometry (DXA), bioelectrical impedance (BIA) and tape measured abdominal circumference (AC)-based equations and from three-dimensional scanning (3DS).

Results

Measures were made of fat-free mass (FFM): 90.5±7.0 (82.0–106.7) kg, where FFM included total body water: 62.8±5.0 (55.8–71.8) L, representing 69±2 (67–73) % of FFM, along with calculated FFM index: 26.8±2.4 (24.4–32.9) kg/m2). DXA measures were made for bone mineral content 4.1±0.4 (3.5–4.9) kg, bone mineral density (BMD) 1.56±0.10 (1.37–1.76) g/cm2and %BF 19.5±6.6 (9.0–27.8). Additional measures of percent body fat (%BF) were made by AC: 20.3±2.9 (15.2–24.6), BIA: 23.7±6.4 (9.8–29.2) and 3DS: 25.5±4.7 (18.9–32.2). AC %BF reasonably matched DXA %BF, with expected overprediction and underprediction at low and high DXA %BF. BIA %BF was affected by deviations from assumed FFM hydration (72%–73%).

Conclusion

These men are classified as obese by BMI but carried massive amounts of muscle and bone on their large frames, while presenting a range of %BF irrelevant to strength performance. BMI did not predict obesity and adiposity had no association with muscle mass and strength performance.
Fast food consumption in adults living in Canada: alternative measurement methods, consumption choices, and correlates
Authors: Seale Emily , de Groh Margaret , Greene-Finestone Linda
Published: November 2022

Global industries and technological advancements have contributed to the proliferation of fast food (FF) establishments and ultraprocessed food, associated with poorer diet quality and health outcomes. To investigate FF as an indicator, we compared alternative methods to capture self-reported FF consumption and examined associated socio-demographic factors. We conducted a secondary analysis of the 2014–2015 Foodbook study, a cross-sectional survey on foods consumed by Canadians during the previous week. An embedded randomized design compared alternative FF intake questions of varying details. A total of 6062 participants aged 18+ were included, representing 24.7 million Canadian adults. Approximately 48% consumed FF in the past week, and of FF consumers, average frequency was twice. Asking broadly about FF intake without examples resulted in significantly lower reported FF intake compared with the two more detailed questions; the latter two were not significantly different. Burgers, pizza, and submarines/sandwiches were most commonly consumed. Men, younger age, higher BMI, women in central Canada (versus territorial regions), and men with income $30 000–$80 000 (versus >$80 000) were associated with higher FF consumption. Consumption of FF is common among Canadians; some associated factors are gender-specific. Further research examining FF as an indicator, and individual and societal implications of FF consumption, is recommended to inform programs and policies.
Test–retest repeatability of electrically evoked isotonic power and isometric torque in the plantar flexors
Authors: Paris Michael T. , Zero Alexander M. , Rice Charles L.
Published: November 2022

Electrically evoked isometric torque has good to excellent repeatability, but the degree of repeatability for electrically evoked isotonic power is unknown. We evaluated the test–retest repeatability of plantar flexion isometric torque and isotonic power evoked using brief tetanic trains at 10 and 50 Hz. Both torque and power had excellent (intraclass correlation coefficient >0.9) repeatability at low and high frequencies. Similar to isometric torque, electrically evoked isotonic power is a stable measure for studying dynamic muscle function.
A comparison of trace element concentrations in chromite from komatiites, picrites, and layered intrusions: implications for the formation of massive chromite layers
Authors: Barnes Sarah-Jane , Mansur Eduardo T. , Maier Wolfgang D. , Prevec Stephen A.
Published: November 2022

By examining the minor and trace element contents of chromites from three intrusions—the Bushveld Complex (South Africa), the Stillwater Complex (USA), and the Great Dyke (Zimbabwe)—and comparing these chromite compositions with those of magmas from which they could have formed (komatiites and picrites) we conclude that ( i) the variations in Ti, V, Sc, and Ga contents across stratigraphy and across individual layers do not support the model of magma mixing leading to chromite-only crystallization, ( ii) the chromites from the lowest levels of the intrusions could have crystallized from komatiite liquids that were contaminated with continental crust, ( iii) the Great Dyke chromites have the highest Cr# and lowest incompatible element contents and formed from a liquid closest to komatiite, ( iv) all of the chromites, except those of the Dunite Succession of the Great Dyke have equilibrated with a liquid that also had crystallized pyroxene, ( v) the Great Dyke and Stillwater chromites show a narrower range in composition than the Bushveld chromites, and ( vi) Chromites from the western limb of the Bushveld Complex contain much higher V contents than all the other chromites. This requires either, that the oxygen fugacity ( fO2) was lower in the western Bushveld or that the chromites equilibrated with a V-rich magma. We favor a model where chromite and silicate minerals crystallized in cotectic proportions (∼2:98). The chromite, silicates, and transporting liquid are emplaced into the magma chamber. During emplacement the chromite and silicate separated due to viscous particle flow to form a massive chromite layer overlain by silicates.
Spatial and temporal genetic stock composition of river herring bycatch in southern New England Atlantic herring and mackerel fisheries
Authors: Reid Kerry , Hoey Jennifer A. , Gahagan Benjamin I. , Schondelmeier Bradley P. , Hasselman Daniel J. , Bowden Alison A. , Armstrong Michael P. , Garza John Carlos , Palkovacs Eric P.
Published: November 2022

Anadromous river herring (alewife and blueback herring) persist at historically low abundances and are caught as bycatch in commercial fisheries, potentially preventing recovery despite conservation efforts. We used newly established single-nucleotide polymorphism genetic baselines for alewife and blueback herring to define fine-scale reporting groups for each species. We then determined the occurrence of fish from these reporting groups in bycatch samples from a Northwest Atlantic fishery over four years. Within sampled bycatch events, the highest proportions of alewife were from the Block Island (34%) and Long Island Sound (22%) reporting groups, while for blueback herring the highest proportions were from the Mid-Atlantic (47%) and Northern New England (24%) reporting groups. We then quantified stock-specific mortality in a focal geographic area (∼3500 km2, including Block Island Sound) of high bycatch incidence and sampling effort, where the most accurate estimates of mortality could be made. During this period, we estimate that bycatch took about 4.6 million alewife and 1.2 million blueback herring, highlighting the need to reduce bycatch mortality for the most depleted river herring stocks.
The SPHERE view of multiple star formation
Authors: Gratton Raffaele , Desidera Silvano , Marzari Francesco , Bonavita Mariangela
Published: November 2022

While a large fraction of the stars are in multiple systems, our understanding of the processes leading to the formation of these systems is still inadequate. Given the large theoretical uncertainties, observation plays a basic role. Here we discuss the contribution of high contrast imaging, and more specifically of the SPHERE instrument at the ESO Very Large Telescope, in this area. SPHERE nicely complements other instruments such as Gaia or ALMA—in detecting and characterizing systems near the peak of the binary distribution with separation and allows to capture snapshots of binary formation within disks that are invaluable for the understanding of disk fragmentation.
First steps of planet formation around very low mass stars and brown dwarfs
Authors: Pinilla Paola
Published: November 2022

Brown dwarfs and very low mass stars are a significant fraction of stars in our galaxy and they are interesting laboratories to investigate planet formation in extreme conditions of low temperature and densities. In addition, the dust radial drift of particles is expected to be a more difficult barrier to overcome during the first steps of planet formation in these disks. ALMA high-angular resolution observations of few protoplanetary disks around BDs and VLMS have shown substructures as in the disks around Sun-like stars. Such observations suggests that giant planets embedded in the disks are the most likely origin of the observed substructures. However, this type of planets represent less than 2% of the confirmed exoplanets so far around all stars, and they are difficult to form by different core accretion models (either pebble or planetesimal accretion). Dedicated deep observations of disks around BDs and VLMS with ALMA and JWST will provide significant progress on understanding the main properties of these objects (e.g., disk size and mass), which is crucial for determining the physical mechanisms that rule the evolution of these disks and the effect on the potential planets that may form in these environments.
On the cosmological constant as a quantum operator
Authors: De Córdoba P. Fernández , Torromé R. Gallego , Gavasso S. , Isidro J. M.
Published: November 2022

We regard the cosmological fluid within an exponentially expanding FLRW spacetime as the probability fluid of a nonrelativistic Schroedinger field. The scalar Schroedinger particle so described has a mass equal to the total (baryonic plus dark) matter content of the Universe. This procedure allows a description of the cosmological fluid by means of the operator formalism of nonrelativistic quantum theory. Under the assumption of radial symmetry, a quantum operator proportional to [Formula: see text] represents the cosmological constant [Formula: see text]. The experimentally measured value of [Formula: see text] is one of the eigenvalues of [Formula: see text]. Next we solve the Poisson equation [Formula: see text] for the gravitational potential [Formula: see text], with the cosmological constant [Formula: see text] playing the role of a source term. It turns out that [Formula: see text] includes, besides the standard Newtonian potential [Formula: see text], a correction term proportional to [Formula: see text] identical to that appearing in theories of modified Newtonian dynamics.
The Unusual Value of Long-Term Studies of Individuals: The Example of the Isle of Rum Red Deer Project
Authors: Pemberton Josephine M. , Kruuk Loeske E.B. , Clutton-Brock Tim
Published: November 2022

Long-term studies of individuals enable incisive investigations of questions across ecology and evolution. Here, we illustrate this claim by reference to our long-term study of red deer on the Isle of Rum, Scotland. This project has established many of the characteristics of social organization, selection, and population ecology typical of large, polygynous, seasonally breeding mammals, with wider implications for our understanding of sexual selection and the evolution of sex differences, as well as for their population dynamics and population management. As molecular genetic techniques have developed, the project has pivoted to investigate evolutionary genetic questions, also breaking new ground in this field. With ongoing advances in genomics and statistical approaches and the development of increasingly sophisticated ways to assay new phenotypic traits, the questions that long-term studies such as the red deer study can answer become both broader and ever more sophisticated. They also offer powerful means of understanding the effects of ongoing climate change on wild populations.
Neuroepithelial Interactions in Cancer
Authors: Ayala Gustavo
Published: November 2022

Nerves not only regulate the homeostasis and energetic metabolism of normal epithelial cells but also are critical for cancer, as cancer recapitulates the biology of neural regulation of epithelial tissues. Cancer cells rarely develop in denervated organs, and denervation affects tumorigenesis, in vivo and in humans. Axonogenesis occurs to supply the new malignant epithelial growth with nerves. Neurogenesis happens later, first in ganglia around organs or the spinal column and subsequently through recruitment of neuroblasts from the central nervous system. The hallmark of this stage is regulation of homeostasis and energetic metabolism. Perineural invasion is the most efficient interaction between cancer cells and nerves. The hallmark of this stage is increased proliferation and decreased apoptosis. Finally, carcinoma cells transdifferentiate into a neuronal profile in search of neural independence. The latter is the last stage in neuroepithelial interactions. Treatments for cancer must address the biology of neural regulation of cancer.
Radiation Testing of Commercial Rechargeable Lithium Polymer Batteries for Small Satellite Applications
Authors: Muçogllava Brunilda , Karim Hashmani Raheem , Çakmakoğlu Selman , Bilge Demirköz M.
Published: November 2022

Commercial off-the-shelf (COTS) electrical components are becoming of interest for small satellite applications due to their accessibility, good performance, and low cost. We quantify the performance of Lithium Polymer (LiPo) COTS batteries under irradiation to assess their reliability. LiPo battery cells with LiCoO2 cathodes, nominal voltages of 3.7 V, and rated capacities of 6000 mAh are irradiated with a 30 MeV proton beam from the Middle East Technical University Defocusing Beamline, which delivers a maximum of 73 krad primary dose. Results show protons cause short-term damage, resulting in up to 17% faster discharge rates, which decreases after six months depending on the cell’s position and primary and secondary deposited dose. Additionally, a consumption rate increase of up to 42% occurs for the cells under prolonged secondary irradiation (1.2 krad). The separating polypropylene layer undergoes thinning and discoloration mainly due to secondary particles like neutrons and gammas. Finally, the LiCoO2 cathode of two batteries show dried polyvinylidene fluoride surface build-up, both potentially caused by discharge in a radioactive environment. Damaged cells do not suffer leakage.
Reduction of ZrO2 in LiCl-Li2O Melt During Electrolysis
Authors: Shishkin Aleksey V. , Shishkin Vladimir Yu. , Nikolaev Andrey Yu. , Pankratov Aleksandr A. , Suzdaltsev Andrey V. , Zaikov Yuriy P.
Published: November 2022

Reduction of spent nuclear fuel (SNF) components to metals during the electrolysis of the LiCl-Li2O melt at 650 °C is extremely important in the framework of the development of fuel reprocessing technology. In the present paper the ZrO2 reduction by lithium during the electrolysis of the LiCl-Li2O melt at 650 °C was studied. Cathode processes on a molybdenum substrate in contact with different ZrO2 samples (powder, pressed pellet, dense ceramic) were analyzed using cyclic voltammetry and electrolysis. It was shown that the appearance of ZrO2 near the molybdenum cathode leads to increasing cathode currents and decreasing lithium oxidation current. Both effects indicate the consumption of reduced lithium for the reduction of ZrO2 samples. In order to analyze the reduction products X-ray phase analysis and scanning electron microscopy were used, and to estimate the reduction degree of ZrO2 samples three methods were tested: dissolution of samples in inorganic acid solution, dissolution of samples in EtOAc/Br2 solution, and carbothermal reduction. It was shown that during the electrolysis of dense samples only the lithium zirconate (Li2ZrO3) was formed at their surfaces, whereas the electrolysis of ZrO2 powder samples resulted in the formation of Li2ZrO3, Zr3O, and ZrO phases.
A Composite State of Charge Estimation for Electric Vehicle Lithium-Ion Batteries Using Back-Propagation Neural Network and Extended Kalman Particle Filter
Authors: Pang Hui , Geng Yuanfei , Liu Xiaofei , Wu Longxing
Published: November 2022

Accurate estimation of battery state of charge (SOC) plays a crucial role for facilitating intelligent battery management system development. Due to the high nonlinear relationship between the battery open-circuit voltage (OCV) and SOC, and the shortcomings of traditional polynomial fitting approach, it is an even more challenging task for predicting battery SOC. To address these challenges, this paper presents a composite SOC estimation approach for lithium-ion batteries using back-propagation neural network (BPNN) and extended Kalman particle filter (EKPF). First, a second order resistance capacitance model is established to make parameters identification of a lithium-ion battery cell using recursive least squares algorithm with forgetting factors (FFRLS) approach. Then, BPNN is used to fit the desired OCV-SOC relationship with relatively high precision. Next, by incorporating the extended Kalman filter (EKF) into the particle filter (PF), an expected EKPF approach is presented to realize the SOC estimation. Last, the performances of SOC estimation using different methods, namely the PF, EKF and the EKPF are compared and analyzed under constant current discharge and urban dynamometer driving schedule working conditions. The experimental results show that the proposed method has higher accuracy and robustness compared to the other two SOC estimation methods.
A Machine Learning Model for Adsorption Energies of Chemical Species Applied to CO2 Electroreduction
Authors: Amaral Paulo H. R. , Torrez-Baptista Alvaro D. , Dionisio Dawany , Lopes Thiago , Meneghini Julio R. , Miranda Caetano R.
Published: November 2022

Machine learning methods are applied to obtain adsorption energies of different chemical species on (100), (111), and (211) FCC surfaces of several transition metals and Pb. Based on information available in databases containing adsorption energies obtained via first-principles calculations, we implemented MLPRegressor, XGBRegressor, Support Vector Regressor, and Stacking machine learning models. The fourth model is created from the combination of the previous three through a Stacking technique. In a broader context, our results showed the robustness of machine learning models and the ability of these methods to speed up the screening materials to specific goals, at a low computational cost. We emphasize the ability of our models to predict the adsorption energy for different systems. Due to their generality of them, we were able to make ion predictions on metallic surfaces, taking into account the influence of different functionals. This capability is of special significance due to the difficulty of calculating the correct energy for charged systems by traditional atomistic simulations. From then on, we made predictions for important chemical species in the CO2 electroreduction process, such as the radical anion CO2
−•, an important intermediary for obtaining new products in view of a negative carbon footprint.
Squarate-Based Metal-Organic Frameworks for Highly Selective and Sensitive Electrochemical Sensing of Dopamine
Authors: Zhang Wen , Zheng Xinyue , Jia Gan , Chi Hongzhong , Lin Bao , Qin Haiying , Xie Haijiao , Yuan Yongjun , Fu Degang
Published: November 2022

Dopamine (DA) is an important catecholamine neurotransmitter associated with learning, depression, addiction, and memory loss with simultaneously coordinating movement and reward-associated behavior. It is very important to design highly effective and sensitive sensors for the detection of DA. However, it remains a challenge for detecting DA to obtain selectively and rapidly sensing materials. In this work, we chose octahedral-coordinated squarate-based MOFs with dense Lewis active centers as electrode materials to investigate the electrochemical performance of dopamine oxidation. The multiple ligand functional groups in squarate-based MOFs enable noncovalent interaction with diols, amines, and phenyl groups of DA molecules through electrostatic, H-bonding, and/or π–π stacking interactions. The modified electrode exhibits a wide linear current response range between 2 μM and 400 μM for DA, and the sensor shows significant selectivity and stability. This work enriches the application library of redox-active squarate compounds and can give us a better comprehension of the design and selection of electrode materials for electrochemical sensing and even more catalysis-related research.
Unveiling the Mystery of Lithium Bis(fluorosulfonyl)imide as a Single Salt in Low-to-Moderate Concentration Electrolytes of Lithium Metal and Lithium-Ion Batteries
Authors: Zhang Sheng S.
Published: November 2022

This work aims to unveil the mystery about the suitability of using lithium bis(fluorosulfonyl)imide (LiFSI) as a single salt in low-to-moderate concentration electrolytes of Li metal and Li-ion batteries by studying the corrosion behavior of Al and stainless steel (SS) in 3:7 (wt) ethylene carbonate/ethyl methyl carbonate electrolytes. It is found that regardless of LiFSI concentrations (0.8–1.8 m), there is a ∼4.3 V vs Li/Li+ of “threshold potential,” above which Al suffers uncontrollable corrosion. This finding is confirmed in graphite/LiNi0.80Co0.15Al0.05O2 pouch cells, however, none of Li/LiNi0.80Co0.10Mn0.10O2 coin cells can be charged to 4.2 V in the first charge. Post-mortem analysis of the failed coin cells reveals that the failure is due to anodic corrosion of the SS spacer. Further study on two types of spacers, made by SS304 and SS316L, indicates that the SS316L spacer is more corrosion resistant, however, it still cannot support batteries for long-life cycling. The suitability for using LiFSI as a single electrolyte solute in Li-ion batteries can be guaranteed as long as, at the cathode, the charge voltage is strictly limited to the “threshold potential” and the SS components are avoided. This conclusion is further verified by using four different sources of LiFSI.
Coulombic Efficiency and Capacity Retention are Not Universal Descriptors of Cell Aging
Authors: Rodrigues Marco-Tulio F.
Published: November 2022

Capacity and coulombic efficiency are often used to assess the performance of Li-ion batteries, under the assumption that these quantities can provide direct insights about the rate of electron consumption due to growth of the solid electrolyte interphase (SEI). Here, we show that electrode properties can actually change the amount of information about aging that can be directly retrieved from capacity measurements. During cycling of full-cells, only portions of the voltage profiles of the positive and negative electrodes are accessible, leaving a reservoir of cyclable Li+ stored at both electrodes. The size and availability of this reservoir depends on the shape of the voltage profiles, and accessing this extra Li+ can offset some of the capacity that is consumed by the SEI. Consequently, capacity and efficiency measurements can, at times, severely underestimate the rate of side reactions experienced by the cell. We show, for example, that a same rate of SEI growth would cause faster capacity fade in LiFePO4 than in NMC cells, and that the perceived effects of aging depend on testing variables such as depth of discharge. Simply measuring capacity may be insufficient to gauge the true extent of aging endured by Li-ion batteries.
Gold Nanoparticles Decorated with Multi-Walled Carbon Nanotubes/Graphene Oxide for Voltammetric Determination of Dopamine in the Presence of Acetaminophen
Authors: Saki Azin , Pourghobadi Zeinab , Derikvand Zohreh
Published: November 2022

We developed an electrochemical sensor by combination of Graphene oxide (GO) and multi-walled carbon nanotubes (MWCNTs) then decorated with Au-nanoparticles (AuNPs) by an electrodeposition process for detection of dopamine (DP) in the presence of acetaminophen (AC). The electrochemical properties of MWCNT/GO- AuNPs/GCE were characterized by scanning electron microscopy (SEM) and cyclic voltammetry (CV).The results displayed that Au nanoparticles were well jointed onto MWCNT/GO nanocomposite. The electrochemical responses displayed the prepared sensor showed enhanced electrocatalytic activity for the detection of DP inthe presence of acetaminophen (AC). Under optimum conditions, the proposed sensorpresented a linear response based on the DP concentration in the range of 1.0 to 165 μM with a detection limit of 0.07 μM using the differential pulse voltammogram (DPV) method.Moreover, this proposed sensor displayed a linear range concentration of AC ranging from 3 to 200.0 μM and detection limit of 0.061 μM. Also, the prepared sensor indicated excellent sensitivity and selectivity for the DP determination in the presence of AC in real samples.
Association between Endothelial Cell-Specific Molecule 1 and Galectin-3 in Patients with ST-Segment Elevation Myocardial Infarction: A Pilot Study
Authors: Wei Peng , Wang Xiaoqing , Fu Qiang , Zong Bin , Liu Xuekui , Zhang Miaomiao , Cao Bangming , Zhu Ke
Published: November 2022

The biomarkers galectin-3 (Gal-3) and endothelial cell-specific molecule 1 (ESM-1) reflect endothelial function and inflammation. As a consequence, they play an important role in both the diagnosis and characterization of ST-segment elevation myocardial infarction (STEMI). However, no prior study has explored the association between ESM-1 and Gal-3 in STEMI patients. This study is aimed at determining the ESM-1 and Gal-3 levels in the serum of STEMI patients and then exploring the correlation between the levels of these two biomarkers and their clinical significance in STEMI patients. The participants were divided into two groups: the ST group comprised 35 hospitalized STEMI patients while the control group comprised 24 people with normal coronary arteries. In all the patients, venous blood was taken from the middle of the antecubital fossa. The serum ESM-1 and Gal-3 concentrations were determined using an enzyme-linked immunosorbent assay. The results revealed that the ESM-1 and Gal-3 levels in the STEMI patients were 1.6 and 2.8 times higher, respectively, when compared with the controls (

P
<
0.001

). Moreover, the ESM-1 and Gal-3 levels exhibited a positive linear correlation (

r
=
0.758

,

P
<
0.001

) in the acute STEMI patients. In conclusion, the ESM-1 and Gal-3 levels were found to be significantly elevated and correlated in the STEMI patients. Thus, combining these two biomarkers of endothelial dysfunction and inflammation might be useful for the diagnosis and assessment of STEMI.
Fundamental Units of Measurement and Extra Dimensions
Authors: Abdukadyrov Askar
Published: November 2022

The space available to our perception is three-dimensional with full evidence. The development of physics led to the hypothesis of extra dimensions. It is believed that an important role in the unification of physics should play by the Planck units of mass, length and time, built on the universal constants

c

(the speed of light in a vacuum),

G

(the gravitational constant), and

ħ

(the reduced Planck constant). In August 2021, published work in which it is shown that the fundamental role in the unification of physics, in fact, was played by the Stoney units, built on the universal constants

c
−
G
−
e

or

c
−
G
−
ħ

and

α

(where e is the elementary electric charge, and α is the fine-structure constant). Using this result, the presented work offers a possible solution to the riddle of extra dimensions; it is shown that any additional spatial dimension can be expressed in terms of the fundamental length or the product of the fundamental time and the speed of light in a vacuum.
Disseminated Mycobacterium Tuberculosis and IgA Nephropathy
Authors: Audley Gordon , Davidson Bianca , Jones Erika , Price Brendon , Rayner Brian , Wearne Nicola , Barday Zibya
Published: November 2022

Mycobacterium tuberculosis (MTB) is an under-recognised cause of genitourinary disease. IgA nephropathy (IgAN), a leading cause of glomerulonephritis worldwide, has been described as a rare consequence of disseminated MTB infection. In this case report, we present the first case of MTB associated IgAN in Africa. Finding IgAN on kidney biopsy in an MTB endemic area should prompt a thorough investigation for MTB to increase the chance of remission of IgAN and prevent inappropriate use of immunosuppression.
Intraosseous Lipoma Mimicking Periapical Lesion: A Rare Presentation
Authors: Bannerjee Abhishek , Ghosh Snehashish , Das Moumalini , Wang Patrick , Ramsridhar Saranya , Patil Shankargouda
Published: November 2022

Lipoma is one of the benign soft-tissue tumors in the adipose tissue. Oral lipomas comprise 1%–5% of benign oral tumors. They are slow-growing, soft, asymptomatic, solitary tumors. In this case report, a 45-year-old female patient having swelling on the upper right arch for 2 months has been reported. Clinically, the right upper second premolar and first molar were grossly carious, with diffuse swelling on the adjacent vestibule. A provisional diagnosis of the periapical abscess was rendered. Radiological evaluation and routine blood tests were performed. After the tissue was obtained, following teeth extraction and socket curettage, it was sent for histopathological evaluation, and findings suggested intraoral intraosseous lipoma. Clinically, they are asymptomatic, and therefore, if it was not curetted and histopathologic evaluation not done, and only thought to be just a swelling or a periapical abscess, proper treatment could not have been established. This paper will surely bring out the importance of histopathology in routine dentistry and the role of histopathological evaluation of periapical soft tissues.
Free Radical Scavenging, Anti-Infectious, and Toxicity Activities from Stenochlaena palustris (Burm.f.) Bedd. Extracts
Authors: Hendra Rudi , Khodijah Rohimatul , Almurdani Muhammad , Haryani Yuli , Nugraha Ari Satia , Frimayanti Neni , Teruna Hilwan Yuda , Abdulah Rizky
Published: November 2022

Stenochlaena palustris (Burm.f.) Bedd. (Blechnaceae) or Kelakai is a traditional medicinal plant found in the Indonesian islands of Borneo and Sumatra. It has been used to treat wound healing, infection, and diabetes. This study looked into the free radical scavenging activity, antiplasmodial activity, toxicity, and antibacterial activity against pathogenic bacteria. The species’ aerial part was extracted with methanol, followed by a liquid-liquid extraction against (n-hexane, dichloromethane, and ethyl acetate). The extracts’ free radical scavenging activities were determined using DPPH and NO radicals. The antiplasmodial and toxicity assays were conducted using two Plasmodium falciparum strains (3D7 and W2) and the brine shrimp lethality test. In addition, antibacterial activity was determined using the well diffusion method. The results revealed that ethyl acetate depicted potential activities toward the assay. The ethyl acetate showed potential free radical scavenging activities with an IC50 value of 51.63 ± 0.46 μg/mL (DPPH) and 60.03 ± 0.65 μg/mL (NO). The antiplasmodial activities showed that the ethyl acetate had potential activities among the extracts with an IC50 value of 11.06 ± 0.45 μg/mL. However, all the extracts demonstrated nontoxic toward Artemia salina with LC50 > 1000 μg/mL. Furthermore, the ethyl acetate demonstrated intermediate susceptibility against B. cereus ATCC 10876, V. parahaemolyticus ATCC 17802, L. monocytogenes ATCC 7644, and S. Typhimurium ATCC 14028 at a concentration of 500 μg/disc. According to these findings, the ethyl acetate extract of S. palustris (Burm.f.) Bedd is a promising source of natural antioxidants and antiplasmodial agents.
Development and Application of Equipment for Anchor Cable with C-Shaped Tube Tension-Shear Test System
Authors: Shan Renliang , Liang Chen , Liu Weijun , Jiang Yuzhao , Li Tianwen
Published: November 2022

Based on the phenomenon of serious tensile-shear failure of bolts and cables, domestic and foreign scholars’ research on the mechanical properties of bolts and cables has gradually changed from pure tensile to tensile-shear performance. To reduce the long-term bolt and cable breakage accidents in deep soft rock tunnels in coal mines, we independently developed a new type of support material—anchor cable with C-shaped tube and a corresponding tensile-shear test system. The system parameters are set through theoretical derivation, and the three main structures of the test system are designed with ANSYS: shear box, vertical loading reaction frame, and horizontal loading reaction frame. The numerical simulation results show that when the thickness of the shear box steel plate is 20 mm, the maximum strain is about 2.7‰. When the diameters of the vertical column and the horizontal bar are 220 mm and 80 mm, respectively, the maximum strains of the column and the horizontal bar are about 0.17‰ and 0.04‰, respectively. The strength and deformation of the three main structures meet the design requirements. The developed test system was tested on-site. The test results show that the system can perform tensile test and two different modes of the double shear test. The main structure has no obvious deformation during the test, meeting the design requirements. In addition, the rational design of the shear box eliminates the error caused by the shear block. The results show that the shear resistance of anchor cable with C-shaped tube is better than that of pure anchor cables. The research results can provide a reference for developing other similar test systems.
Dietary Vitamin A Intake and Circulating Vitamin A Concentrations and the Risk of Three Common Cancers in Women: A Meta-Analysis
Authors: Han Xiaoyong , Zhao Rangyin , Wang Yongfeng , Ma Haizhong , Yu Miao , Chen Xiaohong , Zhang Dongzhi , Ma Shixun , Liu Bin , Cai Hui
Published: November 2022

Background. According to relevant clinical research, dietary and circulating antioxidants vitamin A are connected with the risk of breast, cervical, and ovarian cancer in women. However, there was inconsistency between the findings. We completed this meta-analysis at the right moment to address this contradiction of the problem. Methods. Web of Science, Embase, and PubMed databases were searched using the proposed search strategy and filtered using the inclusion and exclusion criteria as well as the NOS quality score. As of May 2022, low intake or low concentration was used as a control, and odds ratio (OR) or relative risk (RR) and ninety-five percent confidence intervals (95% CI) were extracted for high intake. Stata 12.0 was used to process the data. Results. Our meta-analysis included a total of 49 studies, 29 on breast cancer, 10 on ovarian cancer, and 10 on cervical cancer. There were 38 case-control studies included, with 25,363 cases and 42,281 controls; there were 11 cohort studies included, 1,334,176 individuals were followed up, and finally 9496 obtained cancer. The pooled OR value results were as follows: diet or supplements (

OR
=
0.83

, 95% CI 0.76-0.90,

I

2

=
56.1
%

) and serum or plasma (

OR
=
0.96

, 95% CI 0.86-1.09,

I

2

=
29.5
%

). Subgroup analyses were performed according to cancer type, diet or supplements, serum or plasma, study type, and geographic regions. Conclusions. In North American and Asian populations, high dietary consumption of vitamin A or supplements decreases the incidence of three cancers in women, with breast and ovarian cancers being more significant. However, high circulating vitamin A concentrations were not significantly connected with the risk of the three malignancies.
Design a Multistub Array Antenna at 28 GHz with Beam Switching Ability
Authors: Lak A.
Published: November 2022

In this paper, a Millimeter Wave antenna is designed which has a compact, lightweight and planar configuration. The frequency band is 27–29.5 GHz as a candidate band for 5G/millimeter Wave (mmW) systems. The antenna structure is similar to Quasi Yagi antenna which has driver, director, feeding part, and reflector. Substrate Integrated Waveguide used for feeding part of single element antenna and Wilkinson power divider used for antenna array feeding network. The proposed antenna has been simulated, fabricated, and measured (S11, E, and H pattern). The simulation and measurement values showed good similarity. The switched line phase shifter used to consider the beam steering (rotation) ability of the designed antenna which is important in (mmW) systems such as RADARs and mobile handsets. To evaluate this ability, for

0

°

,

30

°

,

45

°

, and

90

°

phase differences, the beam steering angle (

θ

) simulated and also for

−

90

°

and

90

°

implemented. The results showed that the efficiency, S11, and E patterns in the rotated beam is suitable and without degradation in antenna operation. To simulate and evaluate the designed antenna HFSS and CST Software are used.
C-CAT: The National Datacenter for Cancer Genomic Medicine in Japan
Authors: Kohno Takashi , Kato Mamoru , Kohsaka Shinji , Sudo Tomohisa , Tamai Ikuo , Shiraishi Yuichi , Okuma Yusuke , Ogasawara Daisuke , Suzuki Tatsuya , Yoshida Teruhiko , Mano Hiroyuki
Published: November 2022

Since June 2019, under the umbrella of the national health insurance system, Japan has started cancer genomic medicine (CGM) with comprehensive genomic profiling (CGP) tests. The Ministry of Health, Labour and Welfare (MHLW) of Japan constructed a network of CGM hospitals (a total of 233 institutes as of July 1, 2022) and established the Center for Cancer Genomics and Advanced Therapeutics (C-CAT), the national datacenter for CGM. Clinical information and genomic data from the CGP tests are securely transferred to C-CAT, which then generates “C-CAT Findings” reports containing information of clinical annotation and matched clinical trials based on the CGP data. As of June 30, 2022, a total of 36,340 datapoints of clinical/genomic information are aggregated in C-CAT, and the number is expected to increase swiftly. The data are now open for sharing with not only the CGM hospitals but also other academic institutions and industries.
Lung CAFs Show T Cells the Velvet Rope
Authors: Sherman Mara H.
Published: November 2022

Cancer-associated fibroblasts share defined features with fibroblasts in secondary lymphoid organs, including the ability to regulate immune cell localization. In this issue of Cancer Discovery, Grout and colleagues perform multimodal analysis of human lung cancer specimens and identify two distinct fibroblast populations associated with spatial exclusion of T cells from tumor cell nests.

See related article by Grout et al., p. 2606 (3).
A Therapeutically Targetable NOTCH1–SIRT1–KAT7 Axis in T-cell Leukemia
Authors: Lancho Olga , Singh Amartya , da Silva-Diz Victoria , Aleksandrova Maya , Khatun Jesminara , Tottone Luca , Nunes Patricia Renck , Luo Shirley , Zhao Caifeng , Zheng Haiyan , Chiles Eric , Zuo Zhenyu , Rocha Pedro P. , Su Xiaoyang , Khiabanian Hossein , Herranz Daniel
Published: November 2022

T-cell acute lymphoblastic leukemia (T-ALL) is a NOTCH1-driven disease in need of novel therapies. Here, we identify a NOTCH1–SIRT1–KAT7 link as a therapeutic vulnerability in T-ALL, in which the histone deacetylase SIRT1 is overexpressed downstream of a NOTCH1-bound enhancer. SIRT1 loss impaired leukemia generation, whereas SIRT1 overexpression accelerated leukemia and conferred resistance to NOTCH1 inhibition in a deacetylase-dependent manner. Moreover, pharmacologic or genetic inhibition of SIRT1 resulted in significant antileukemic effects. Global acetyl proteomics upon SIRT1 loss uncovered hyperacetylation of KAT7 and BRD1, subunits of a histone acetyltransferase complex targeting H4K12. Metabolic and gene-expression profiling revealed metabolic changes together with a transcriptional signature resembling KAT7 deletion. Consistently, SIRT1 loss resulted in reduced H4K12ac, and overexpression of a nonacetylatable KAT7-mutant partly rescued SIRT1 loss-induced proliferation defects. Overall, our results uncover therapeutic targets in T-ALL and reveal a circular feedback mechanism balancing deacetylase/acetyltransferase activation with potentially broad relevance in cancer.

Significance:

We identify a T-ALL axis whereby NOTCH1 activates SIRT1 through an enhancer region, and SIRT1 deacetylates and activates KAT7. Targeting SIRT1 shows antileukemic effects, partly mediated by KAT7 inactivation. Our results reveal T-ALL therapeutic targets and uncover a rheostat mechanism between deacetylase/acetyltransferase activities with potentially broader cancer relevance.

This article is highlighted in the In This Issue feature, p. 1