bluuebunny/crossref_metadata_2025 huggingface dataset:
Combinatorial physicochemical stimuli in the three-dimensional environment of a hyaluronic acid hydrogel amplify chondrogenesis by stimulating phosphorylation of the Smad and MAPK signaling pathways
Authors: Ahn Jinsung , Arai Yoshie , Kim Byoung Ju , Seo Young-Kwon , Moon James J. , Shin Dong Ah , Choi Bogyu , Lee Soo-Hong
Published: June 2022

The chondrogenesis of stem cells and cartilage tissue regeneration are more efficient in a three-dimensional (3D) environment than in a two-dimensional (2D) environment. Although extensive studies have examined the effects of biochemical or physical cues alone, it is not fully understood how these biochemical and biophysical cues in the 3D environment are intertwined and orchestrated with chondrogenesis for cartilage tissue regeneration. In this study, we used photocrosslinked hyaluronic acid (HA), the extracellular matrix of cartilage, as a general 3D microenvironment to characterize the effects of dimensionality, localization of biochemical cues, regulation of biophysical cues, and external stimulation on chondrogenic signaling pathways in adipose-derived stem cells (hASCs). TGF-β3 was immobilized in HA hydrogels by ionic or covalent conjugation. The stiffness of the hydrogels was tuned by varying the crosslinking density, and an external stimulus for chondrogenesis was provided by ultrasound. The results revealed that the levels of chondrogenic signals in hASCs cultured in the 3D HA hydrogel depended on the presence of TGF-β3, and a reduction in the stiffness of the TGF-β3 covalent conjugated hydrogel increased the chance of interaction with encapsulated hASCs, leading to an increase in chondrogenic signals. External stimulation with ultrasound increased the interaction of hASCs with HA via CD44, thereby increasing chondrogenesis. Our results present a new understanding of the intertwined mechanisms of chondrogenesis in 3D hydrogels connecting TGF-β3 sequestration, mechanical properties, and ultrasound-based external stimulation. Overall, our results suggest that when designing novel biomaterials for tissue engineering, it is necessary to consider the combinatorial mechanism of action in 3D microenvironments.
Diversity of spatiotemporal coding reveals specialized visual processing streams in the mouse cortex
Authors: Han Xu , Vermaercke Ben , Bonin Vincent
Published: June 2022

The cerebral cortex contains diverse neural representations of the visual scene, each enabling distinct visual and spatial abilities. However, the extent to which representations are distributed or segregated across cortical areas remains poorly understood. By determining the spatial and temporal responses of >30,000 layer 2/3 pyramidal neurons, we characterize the functional organization of parallel visual streams across eight areas of the mouse cortex. While dorsal and ventral areas form complementary representations of spatiotemporal frequency, motion speed, and spatial patterns, the anterior and posterior dorsal areas show distinct specializations for fast and slow oriented contrasts. At the cellular level, while diverse spatiotemporal tuning lies along a continuum, oriented and non-oriented spatial patterns are encoded by distinct tuning types. The identified tuning types are present across dorsal and ventral streams. The data underscore the highly specific and highly distributed nature of visual cortical representations, which drives specialization of cortical areas and streams.
Cross-sectional seroprevalence surveys of SARS-CoV-2 antibodies in children in Germany, June 2020 to May 2021
Authors: Sorg Anna-Lisa , Bergfeld Leon , Jank Marietta , Corman Victor , Semmler Ilia , Goertz Anna , Beyerlein Andreas , Verjans Eva , Wagner Norbert , Von Bernuth Horst , Lander Fabian , Weil Katharina , Hufnagel Markus , Spiekerkoetter Ute , Chao Cho-Ming , Naehrlich Lutz , Muntau Ania Carolina , Schulze-Sturm Ulf , Hansen Gesine , Wetzke Martin , Jung Anna-Maria , Niehues Tim , Fricke-Otto Susanne , Von Both Ulrich , Huebner Johannes , Behrends Uta , Liese Johannes G. , Schwerk Christian , Drosten Christian , Von Kries Ruediger , Schroten Horst
Published: June 2022

The rate of SARS-CoV-2 infections in children remains unclear due to many asymptomatic cases. We present a study of cross-sectional seroprevalence surveys of anti-SARS-CoV-2 IgG in 10,358 children recruited in paediatric hospitals across Germany from June 2020 to May 2021. Seropositivity increased from 2.0% (95% CI 1.6, 2.5) to 10.8% (95% CI 8.7, 12.9) in March 2021 with little change up to May 2021. Rates increased by migrant background (2.8%, 4.4% and 7.8% for no, one and two parents born outside Germany). Children under three were initially 3.6 (95% CI 2.3, 5.7) times more likely to be seropositive with levels equalising later. The ratio of seropositive cases per recalled infection decreased from 8.6 to 2.8. Since seropositivity exceeds the rate of recalled infections considerably, serologic testing may provide a more valid estimate of infections, which is required to assess both the spread and the risk for severe outcomes of SARS-CoV-2 infections.
Experimental demonstration of highly reliable dynamic memristor for artificial neuron and neuromorphic computing
Authors: Park See-On , Jeong Hakcheon , Park Jongyong , Bae Jongmin , Choi Shinhyun
Published: June 2022

Neuromorphic computing, a computing paradigm inspired by the human brain, enables energy-efficient and fast artificial neural networks. To process information, neuromorphic computing directly mimics the operation of biological neurons in a human brain. To effectively imitate biological neurons with electrical devices, memristor-based artificial neurons attract attention because of their simple structure, energy efficiency, and excellent scalability. However, memristor’s non-reliability issues have been one of the main obstacles for the development of memristor-based artificial neurons and neuromorphic computings. Here, we show a memristor 1R cross-bar array without transistor devices for individual memristor access with low variation, 100% yield, large dynamic range, and fast speed for artificial neuron and neuromorphic computing. Based on the developed memristor, we experimentally demonstrate a memristor-based neuron with leaky-integrate and fire property with excellent reliability. Furthermore, we develop a neuro-memristive computing system based on the short-term memory effect of the developed memristor for efficient processing of sequential data. Our neuro-memristive computing system successfully trains and generates bio-medical sequential data (antimicrobial peptides) while using a small number of training parameters. Our results open up the possibility of memristor-based artificial neurons and neuromorphic computing systems, which are essential for energy-efficient edge computing devices.
Ex vivo-expanded human CD19+TIM-1+ regulatory B cells suppress immune responses in vivo and are dependent upon the TIM-1/STAT3 axis
Authors: Shankar S. , Stolp J. , Juvet S. C. , Beckett J. , Macklin P. S. , Issa F. , Hester J. , Wood K. J.
Published: June 2022

Regulatory B cells (Breg) are a heterogenous population with immune-modulating functions. The rarity of human IL-10+ Breg makes translational studies difficult. Here we report ex vivo expansion of human B cells with in vivo regulatory function (expBreg). CD154-stimulation of human CD19+ B cells drives >900-fold expansion of IL-10+ B cells that is maintained in culture for 14 days. Whilst expBreg-mediated suppressive function is partially dependent on IL-10 expression, CRISPR-mediated gene deletions demonstrate predominant roles for TIM-1 and CD154. TIM-1 regulates STAT3 signalling and modulates downstream suppressive function. In a clinically relevant humanised mouse model of skin transplantation, expBreg prolongs human allograft survival. Meanwhile, CD19+CD73-CD25+CD71+TIM-1+CD154+ Breg cells are enriched in the peripheral blood of human donors with cutaneous squamous cell carcinoma (SCC). TIM-1+ and pSTAT3+ B cells are also identified in B cell clusters within histological sections of human cutaneous SCC tumours. Our findings thus provide insights on Breg homoeostasis and present possible targets for Breg-related therapies.
A continuum of bright and dark-pulse states in a photonic-crystal resonator
Authors: Yu Su-Peng , Lucas Erwan , Zang Jizhao , Papp Scott B.
Published: June 2022

Nonlinearity is a powerful determinant of physical systems. Controlling nonlinearity leads to interesting states of matter and new applications. In optics, diverse families of continuous and discrete states arise from balance of nonlinearity and group-velocity dispersion (GVD). Moreover, the dichotomy of states with locally enhanced or diminished field intensity depends critically on the relative sign of nonlinearity and either anomalous or normal GVD. Here, we introduce a resonator with unconditionally normal GVD and a single defect mode that supports both dark, reduced-intensity states and bright, enhanced-intensity states. We access and explore this dark-to-bright pulse continuum by phase-matching with a photonic-crystal resonator, which mediates the competition of nonlinearity and normal GVD. These stationary temporal states are coherent frequency combs, featuring highly designable spectra and ultralow noise repetition-frequency and intensity characteristics. The dark-to-bright continuum illuminates physical roles of Kerr nonlinearity, GVD, and laser propagation in a gapped nanophotonic medium.
Integrative epigenomic and transcriptomic analysis reveals the requirement of JUNB for hematopoietic fate induction
Authors: Chen Xia , Wang Peiliang , Qiu Hui , Zhu Yonglin , Zhang Xingwu , Zhang Yaxuan , Duan Fuyu , Ding Shuangyuan , Guo Jianying , Huang Yue , Na Jie
Published: June 2022

Human pluripotent stem cell differentiation towards hematopoietic progenitor cell can serve as an in vitro model for human embryonic hematopoiesis, but the dynamic change of epigenome and transcriptome remains elusive. Here, we systematically profile the chromatin accessibility, H3K4me3 and H3K27me3 modifications, and the transcriptome of intermediate progenitors during hematopoietic progenitor cell differentiation in vitro. The integrative analyses reveal sequential opening-up of regions for the binding of hematopoietic transcription factors and stepwise epigenetic reprogramming of bivalent genes. Single-cell analysis of cells undergoing the endothelial-to-hematopoietic transition and comparison with in vivo hemogenic endothelial cells reveal important features of in vitro and in vivo hematopoiesis. We find that JUNB is an essential regulator for hemogenic endothelium specialization and endothelial-to-hematopoietic transition. These studies depict an epigenomic roadmap from human pluripotent stem cells to hematopoietic progenitor cells, which may pave the way to generate hematopoietic progenitor cells with improved developmental potentials.
Designing 1D correlated-electron states by non-Euclidean topography of 2D monolayers
Authors: Gupta Sunny , Yu Henry , Yakobson Boris I.
Published: June 2022

Two-dimensional (2D) bilayers, twisted to particular angles to display electronic flat bands, are being extensively explored for physics of strongly correlated 2D systems. However, the similar rich physics of one-dimensional (1D) strongly correlated systems remains elusive as it is largely inaccessible by twists. Here, a distinctive way to create 1D flat bands is proposed, by either stamping or growing a 2D monolayer on a non-Euclidean topography-patterned surface. Using boron nitride (hBN) as an example, our analysis employing elastic plate theory, density-functional and coarse-grained tight-binding method reveals that hBN’s bi-periodic sinusoidal deformation creates pseudo- electric and magnetic fields with unexpected spatial dependence. A combination of these fields leads to anisotropic confinement and 1D flat bands. Moreover, changing the periodic undulations can tune the bandwidth, to drive the system to different strongly correlated regimes such as density waves, Luttinger liquid, and Mott insulator. The 1D nature of these states differs from those obtained in twisted materials and can be exploited to study the exciting physics of 1D quantum systems.
On the damage tolerance of 3-D printed Mg-Ti interpenetrating-phase composites with bioinspired architectures
Authors: Zhang Mingyang , Zhao Ning , Yu Qin , Liu Zengqian , Qu Ruitao , Zhang Jian , Li Shujun , Ren Dechun , Berto Filippo , Zhang Zhefeng , Ritchie Robert O.
Published: June 2022

Bioinspired architectures are effective in enhancing the mechanical properties of materials, yet are difficult to construct in metallic systems. The structure-property relationships of bioinspired metallic composites also remain unclear. Here, Mg-Ti composites were fabricated by pressureless infiltrating pure Mg melt into three-dimensional (3-D) printed Ti-6Al-4V scaffolds. The result was composite materials where the constituents are continuous, mutually interpenetrated in 3-D space and exhibit specific spatial arrangements with bioinspired brick-and-mortar, Bouligand, and crossed-lamellar architectures. These architectures promote effective stress transfer, delocalize damage and arrest cracking, thereby bestowing improved strength and ductility than composites with discrete reinforcements. Additionally, they activate a series of extrinsic toughening mechanisms, including crack deflection/twist and uncracked-ligament bridging, which enable crack-tip shielding from the applied stress and lead to “Γ”-shaped rising fracture resistance R-curves. Quantitative relationships were established for the stiffness and strengths of the composites by adapting classical laminate theory to incorporate their architectural characteristics.
Estrogen receptor positive breast cancers have patient specific hormone sensitivities and rely on progesterone receptor
Authors: Scabia Valentina , Ayyanan Ayyakkannu , De Martino Fabio , Agnoletto Andrea , Battista Laura , Laszlo Csaba , Treboux Assia , Zaman Khalil , Stravodimou Athina , Jallut Didier , Fiche Maryse , Bucher Philip , Ambrosini Giovanna , Sflomos George , Brisken Cathrin
Published: June 2022

Estrogen and progesterone receptor (ER, PR) signaling control breast development and impinge on breast carcinogenesis. ER is an established driver of ER + disease but the role of the PR, itself an ER target gene, is debated. We assess the issue in clinically relevant settings by a genetic approach and inject ER + breast cancer cell lines and patient-derived tumor cells to the milk ducts of immunocompromised mice. Such ER + xenografts were exposed to physiologically relevant levels of 17-β-estradiol (E2) and progesterone (P4). We find that independently both premenopausal E2 and P4 levels increase tumor growth and combined treatment enhances metastatic spread. The proliferative responses are patient-specific with MYC and androgen receptor (AR) signatures determining P4 response. PR is required for tumor growth in patient samples and sufficient to drive tumor growth and metastasis in ER signaling ablated tumor cells. Our findings suggest that endocrine therapy may need to be personalized, and that abrogating PR expression can be a therapeutic option.
Sotigalimab and/or nivolumab with chemotherapy in first-line metastatic pancreatic cancer: clinical and immunologic analyses from the randomized phase 2 PRINCE trial
Authors: Padrón Lacey J. , Maurer Deena M. , O’Hara Mark H. , O’Reilly Eileen M. , Wolff Robert A. , Wainberg Zev A. , Ko Andrew H. , Fisher George , Rahma Osama , Lyman Jaclyn P. , Cabanski Christopher R. , Yu Jia Xin , Pfeiffer Shannon M. , Spasic Marko , Xu Jingying , Gherardini Pier Federico , Karakunnel Joyson , Mick Rosemarie , Alanio Cécile , Byrne Katelyn T. , Hollmann Travis J. , Moore Jonni S. , Jones Derek D. , Tognetti Marco , Chen Richard O. , Yang Xiaodong , Salvador Lisa , Wherry E. John , Dugan Ute , O’Donnell-Tormey Jill , Butterfield Lisa H. , Hubbard-Lucey Vanessa M. , Ibrahim Ramy , Fairchild Justin , Bucktrout Samantha , LaVallee Theresa M. , Vonderheide Robert H.
Published: June 2022

Chemotherapy combined with immunotherapy has improved the treatment of certain solid tumors, but effective regimens remain elusive for pancreatic ductal adenocarcinoma (PDAC). We conducted a randomized phase 2 trial evaluating the efficacy of nivolumab (nivo; anti-PD-1) and/or sotigalimab (sotiga; CD40 agonistic antibody) with gemcitabine/nab-paclitaxel (chemotherapy) in patients with first-line metastatic PDAC (NCT03214250). In 105 patients analyzed for efficacy, the primary endpoint of 1-year overall survival (OS) was met for nivo/chemo (57.7%, P = 0.006 compared to historical 1-year OS of 35%, n = 34) but was not met for sotiga/chemo (48.1%, P = 0.062, n = 36) or sotiga/nivo/chemo (41.3%, P = 0.223, n = 35). Secondary endpoints were progression-free survival, objective response rate, disease control rate, duration of response and safety. Treatment-related adverse event rates were similar across arms. Multi-omic circulating and tumor biomarker analyses identified distinct immune signatures associated with survival for nivo/chemo and sotiga/chemo. Survival after nivo/chemo correlated with a less suppressive tumor microenvironment and higher numbers of activated, antigen-experienced circulating T cells at baseline. Survival after sotiga/chemo correlated with greater intratumoral CD4 T cell infiltration and circulating differentiated CD4 T cells and antigen-presenting cells. A patient subset benefitting from sotiga/nivo/chemo was not identified. Collectively, these analyses suggest potential treatment-specific correlates of efficacy and may enable biomarker-selected patient populations in subsequent PDAC chemoimmunotherapy trials.
Hypoxia promotes a perinatal-like progenitor state in the adult murine epicardium
Authors: Sayed Angeliqua , Turoczi Szimonetta , Soares-da-Silva Francisca , Marazzi Giovanna , Hulot Jean-Sebastien , Sassoon David , Valente Mariana
Published: June 2022

The epicardium is a reservoir of progenitors that give rise to coronary vasculature and stroma during development and mediates cardiac vascular repair. However, its role as a source of progenitors in the adult mammalian heart remains unclear due to lack of clear lineage markers and single-cell culture systems to elucidate epicardial progeny cell fate. We found that in vivo exposure of mice to physiological hypoxia induced adult epicardial cells to re-enter the cell cycle and to express a subset of developmental genes. Multiplex single cell transcriptional profiling revealed a lineage relationship between epicardial cells and smooth muscle, stromal cells, as well as cells with an endothelial-like fate. We found that physiological hypoxia promoted a perinatal-like progenitor state in the adult murine epicardium. In vitro clonal analyses of purified epicardial cells showed that cell growth and subsequent differentiation is dependent upon hypoxia, and that resident epicardial cells retain progenitor identity in the adult mammalian heart with self-renewal and multilineage differentiation potential. These results point to a source of progenitor cells in the adult heart that can be stimulated in vivo and provide an in vitro model for further studies.
Bilateral adrenal uptake of 123I MIBG scintigraphy with mild catecholamine elevation, the diagnostic dilemma, and its characteristics
Authors: Inaba Yuiko , Yamamoto Masaaki , Urai Shin , Suzuki Masaki , Nishikage Seiji , Kanzawa Maki , Aoyama Yayoi , Kanda Tomonori , Shigemura Katsumi , Bando Hironori , Iguchi Genzo , Nakamura Yasuhiro , Fujisawa Masato , Imagawa Akihisa , Fukuoka Hidenori , Ogawa Wataru
Published: June 2022

Cases in which bilateral adrenal 123I-Metaiodobenzylguanidine (123I-MIBG) scintigraphy accumulation is sometimes shown, with mildly elevated catecholamine (CA) or metanephrine (MN) levels (within 3 times the upper reference limit) are diagnostic dilemmas. We experienced 3 cases of adrenal incidentalomas with this dilemma in the differential diagnosis. The clinical diagnosis was subclinical Cushing's syndrome in 2 cases, and primary aldosteronism in 1. Despite suspected CA excess in clinical symptoms and imaging findings, the pathological findings of all these tumors were revealed to be cytochrome P450 family 11 subfamily B member 1 (CYP11B1) positive adrenocortical adenomas. Interestingly, adrenal medullary hyperplasia (AMH) was detected in the adrenal parenchyma of all those backgrounds. To clarify the clinical features of such cases, a cross-sectional study was conducted at the Kobe University Hospital from 2014 to 2020. One-hundred sixty-four patients who had undergone 123I-MIBG scintigraphy were recruited. Among them, 10 patients (6.1%) met the above criteria, including the presented 3 cases. Plasma adrenaline, noradrenaline, urinary metanephrine, and normetanephrine had values of 0.05 ± 0.05 ng/mL, 0.63 ± 0.32 ng/mL, 0.22 ± 0.05 mg/day, and 0.35 ± 0.16 mg/day, respectively. Nine cases were complicated with hypertension, and symptoms related to CA excess were observed. Half of them (5 cases) including presented 3 cases had unilateral adrenal tumors. These suggest that in cases of bilateral adrenal uptake on 123I-MIBG, AMH needs to be considered. Adrenocortical adenomas may be associated with AMH and further larger investigation is needed for this pathology.
Identification of ADS024, a newly characterized strain of Bacillus velezensis with direct Clostridiodes difficile killing and toxin degradation bio-activities
Authors: O’Donnell Michelle M. , Hegarty James W. , Healy Brian , Schulz Sarah , Walsh Calum J. , Hill Colin , Ross R. Paul , Rea Mary C. , Farquhar Ronald , Chesnel Laurent
Published: June 2022

Clostridioides difficile infection (CDI) remains a significant health threat worldwide. C. difficile is an opportunistic, toxigenic pathogen that takes advantage of a disrupted gut microbiome to grow and produce signs and symptoms ranging from diarrhea to pseudomembranous colitis. Antibiotics used to treat C. difficile infection are usually broad spectrum and can further disrupt the commensal gut microbiota, leaving patients susceptible to recurrent C. difficile infection. There is a growing need for therapeutic options that can continue to inhibit the outgrowth of C. difficile after antibiotic treatment is completed. Treatments that degrade C. difficile toxins while having minimal collateral impact on gut bacteria are also needed to prevent recurrence. Therapeutic bacteria capable of producing a range of antimicrobial compounds, proteases, and other bioactive metabolites represent a potentially powerful tool for preventing CDI recurrence following resolution of symptoms. Here, we describe the identification and initial characterization of ADS024 (formerly ART24), a novel therapeutic bacterium that can kill C. difficile in vitro with limited impact on other commensal bacteria. In addition to directly killing C. difficile, ADS024 also produces proteases capable of degrading C. difficile toxins, the drivers of symptoms associated with most cases of CDI. ADS024 is in clinical development for the prevention of CDI recurrence as a single-strain live biotherapeutic product, and this initial data set supports further studies aimed at evaluating ADS024 in future human clinical trials.
Analysis of a q-deformed hyperbolic short laser pulse in a multi-level atomic system
Authors: Boutabba N. , Grira S. , Eleuch H.
Published: June 2022

A fast laser pulse with a q-deformed hyperbolic function shape is investigated in a Multi-level atomic system. Therefore, we first derive the exact solution of the Bloch equations describing a two-level atom excited by a q-deformed laser pulse with dephasing and time-dependent detuning. Next, we analyze the dynamic of the atomic population inversion at resonance and off-resonance of a Rubidium 87 three-level atom driven by a classical weak field and a strong q-deformed control laser. Finally, in order to get a deeper insight of the probe field’s absorption and dispersion properties, we investigate the coherence’s dependence on the q-deformation. Our work demonstrates that, the dynamic of the atomic system can be fully controlled through the manipulation of the asymmetry scaling parameter q of the q-deformed hyperbolic laser wave-form.
Artificial neural network prediction of performance and emissions of a diesel engine fueled with palm biodiesel
Authors: El-Shafay A. S. , Alqsair Umar F. , Abdel Razek S. M. , Gad M. S.
Published: June 2022

Increasing of energy consumption, depletion of petroleum fuels and harmful emissions have triggered the interest to find substitute fuels for diesel engines. Palm ethyl ester was synthesized from palm oil through transesterification process. The physicochemical properties of palm biodiesel have been measured and confirmed in accordance with ASTM standards. The aim of the paper is to show the effect of different diesel-palm biodiesel blends on performance, combustion and emissions in diesel engine at engine load variation. Artificial Neural Network was used for the prediction of engine performance, exhaust emission and combustion characteristics parameters. Palm ethyl ester and diesel oil were blended in 5, 10, 15 and 20 by volume percentage. The maximum decreases in thermal efficiency, fuel–air equivalence ratio for B20 were 1.5, 3.5, 6 and 8% but the maximum increases in BSFC, exhaust gas temperature and NOx emission for B20 at full load about diesel fuel were 9, 8 and 10%, respectively. The highest decreases in CO, HC and smoke emissions of B20 about diesel oil at full load were 2, 35 and 18.5% at full load, respectively. Biodiesel blend B20 achieved the maximum declines in peak HRR, cylinder temperature and combustion duration about diesel fuel. The results of ANN were compared with experimental results and showed that ANN is effective modeling method with high accuracy. Palm biodiesel blends up to 20% showed the highest enhancements in engine performance, combustion and emission reductions compared to diesel fuel.
Image analysis reveals molecularly distinct patterns of TILs in NSCLC associated with treatment outcome
Authors: Ding Ruiwen , Prasanna Prateek , Corredor Germán , Barrera Cristian , Zens Philipp , Lu Cheng , Velu Priya , Leo Patrick , Beig Niha , Li Haojia , Toro Paula , Berezowska Sabina , Baxi Vipul , Balli David , Belete Merzu , Rimm David L. , Velcheti Vamsidhar , Schalper Kurt , Madabhushi Anant
Published: June 2022

Despite known histological, biological, and clinical differences between lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC), relatively little is known about the spatial differences in their corresponding immune contextures. Our study of over 1000 LUAD and LUSC tumors revealed that computationally derived patterns of tumor-infiltrating lymphocytes (TILs) on H&E images were different between LUAD (N = 421) and LUSC (N = 438), with TIL density being prognostic of overall survival in LUAD and spatial arrangement being more prognostically relevant in LUSC. In addition, the LUAD-specific TIL signature was associated with OS in an external validation set of 100 NSCLC treated with more than six different neoadjuvant chemotherapy regimens, and predictive of response to therapy in the clinical trial CA209-057 (n = 303). In LUAD, the prognostic TIL signature was primarily comprised of CD4+T and CD8+T cells, whereas in LUSC, the immune patterns were comprised of CD4+T, CD8+T, and CD20+B cells. In both subtypes, prognostic TIL features were associated with transcriptomics-derived immune scores and biological pathways implicated in immune recognition, response, and evasion. Our results suggest the need for histologic subtype-specific TIL-based models for stratifying survival risk and predicting response to therapy. Our findings suggest that predictive models for response to therapy will need to account for the unique morphologic and molecular immune patterns as a function of histologic subtype of NSCLC.
Zinc is a master-regulator of sperm function associated with binding, motility, and metabolic modulation during porcine sperm capacitation
Authors: Zigo Michal , Kerns Karl , Sen Sidharth , Essien Clement , Oko Richard , Xu Dong , Sutovsky Peter
Published: June 2022

Sperm capacitation is a post-testicular maturation step endowing spermatozoa with fertilizing capacity within the female reproductive tract, significant for fertility, reproductive health, and contraception. Recently discovered mammalian sperm zinc signatures and their changes during sperm in vitro capacitation (IVC) warranted a more in-depth study of zinc interacting proteins (further zincoproteins). Here, we identified 1752 zincoproteins, with 102 changing significantly in abundance (P < 0.05) after IVC. These are distributed across 8 molecular functions, 16 biological processes, and 22 protein classes representing 130 pathways. Two key, paradigm-shifting observations were made: i) during sperm capacitation, molecular functions of zincoproteins are both upregulated and downregulated within several molecular function categories; and ii) Huntington’s and Parkinson’s disease pathways were the two most represented, making spermatozoon a candidate model for studying neurodegenerative diseases. These findings highlight the importance of Zn2+homeostasis in reproduction, offering new avenues in semen processing for human-assisted reproductive therapy, identification of somatic-reproductive comorbidities, and livestock breeding.
Bioconversion of CO to formate by artificially designed carbon monoxide:formate oxidoreductase in hyperthermophilic archaea
Authors: Lim Jae Kyu , Yang Ji-In , Kim Yun Jae , Park Yeong-Jun , Kim Yong Hwan
Published: June 2022

Ferredoxin-dependent metabolic engineering of electron transfer circuits has been developed to enhance redox efficiency in the field of synthetic biology, e.g., for hydrogen production and for reduction of flavoproteins or NAD(P)+. Here, we present the bioconversion of carbon monoxide (CO) gas to formate via a synthetic CO:formate oxidoreductase (CFOR), designed as an enzyme complex for direct electron transfer between non-interacting CO dehydrogenase and formate dehydrogenase using an electron-transferring Fe-S fusion protein. The CFOR-introduced Thermococcus onnurineus mutant strains showed CO-dependent formate production in vivo and in vitro. The maximum formate production rate from purified CFOR complex and specific formate productivity from the bioreactor were 2.2 ± 0.2 μmol/mg/min and 73.1 ± 29.0 mmol/g-cells/h, respectively. The CO-dependent CO2 reduction/formate production activity of synthetic CFOR was confirmed, indicating that direct electron transfer between two unrelated dehydrogenases was feasible via mediation of the FeS-FeS fusion protein.
Influent pollutant monitoring in decentralised treatment facilities using electrical conductivity sensors: experimental and modelling insights
Authors: Yu Qiangqiang , Liu Rui , Liang Zhiwei , Li Chenhui , Song Xiaoyan , Ye Linyi , Chen Lujun
Published: June 2022

Electrical conductivity (EC) is a common and cheap water monitoring sensor, which to some extent reflects the water body pollution level qualitatively.
Analysis of sugars and sweeteners via terahertz time-domain spectroscopy
Authors: da Silva Igor J. G. , Raimundo Ivo M. , Mizaikoff Boris
Published: June 2022

The potential of THz spectroscopy in the development of analytical applications for saccharide identification.
Sign control of circularly polarized luminescence of chiral Schiff-base Zn(ii) complexes through coordination geometry changes
Authors: Ikeshita Masahiro , Mizugaki Momo , Ishikawa Takahiro , Matsudaira Kana , Kitahara Maho , Imai Yoshitane , Tsuno Takashi
Published: June 2022

The sign of circularly polarized luminescence (CPL) of chiral Schiff-base Zn(ii) complexes is successfully controlled by coordination geometry changes.
Semiconducting silicon–phosphorus frameworks for caging exotic polycations
Authors: Yox Philip , Porter Andrew P. , Dorn Rick W. , Kyveryga Victoria , Rossini Aaron J. , Kovnir Kirill
Published: June 2022

Silicon phosphides with a new structure have been synthesized. These salt inclusion materials contain exotic polycations such as [Ba6Cl]11+. The structure and properties are investigated.
Highly efficient OER catalyst enabled by in situ generated manganese spinel on polyaniline with strong coordination
Authors: Duan Yanjie , Huang Zhixiong , Ren Jingyu , Dong Xiangbin , Wu Qingsheng , Jia Runping , Xu Xiaowei , Shi Shaojun , Han Sheng
Published: June 2022

Schematic diagram of the Mn3O4/PANI nanocomposite synthesis.
Accelerating research on novel photovoltaic materials
Authors: Unold Thomas
Published: June 2022

Massive increase of data sharing and full utilization of digitization is proposed to help accelerate novel PV material development.
Effect of (3-aminopropyl)triethoxysilane on dissolution of silica nanoparticles synthesized via reverse micro emulsion
Authors: Kang Hyunho , Lee Jihyeon , O'Keefe Tana , Tuga Beza , Hogan Jr. Christopher J. , Haynes Christy L.
Published: June 2022

Silica nanoparticles were designed with varying locations of amine functional groups to characterize their dissolution properties for use in biomedical and agricultural applications.
Atomic-scale detection of individual lead clusters confined in Linde Type A zeolites
Authors: Fatermans Jarmo , Romolini Giacomo , Altantzis Thomas , Hofkens Johan , Roeffaers Maarten B. J. , Bals Sara , Van Aert Sandra
Published: June 2022

By combining TEM with image simulations and XRD, a strategy is proposed for enabling local detection of confined Pb clusters in Linde Type A zeolites with Pb loadings as low as 5 wt%.
Pyrazine-cored covalent organic frameworks for efficient CO2 adsorption and removal of organic dyes
Authors: Hu Guishan , Cui Gang , Zhao Jie , Han Minying , Zou Ru-Yi
Published: June 2022

Two pyrazine-cored COFs have been synthesized, and show high CO2 uptake and rapid adsorption equilibrium and high adsorption capacity for rhodamine B, methylene blue, Congo red and gentian violet.
Cuprous ions can disrupt the structure and functions of the RING finger domain of RNF11
Authors: Wang Yu , Hu Hongze , Yuan Siming , Li Yunyan , Cao Kaiming , Sun Hongbin , Liu Yangzhong
Published: June 2022

Cu(i) can substitute Zn(ii) in the RING-domain of RNF11, which perturbs the protein structure, disrupts protein complexes, and interferes with transcriptional regulation of RNF11 in cells.
A novel copper metal–organic framework catalyst for the highly efficient conversion of CO2 with propargylic amines
Authors: Xu Xiao , Li Zhentao , Huang Huilin , Jing Xu , Duan Chunying
Published: June 2022

A novel copper metal–organic framework catalyst for the highly efficient conversion of carbon dioxide with propargylic amines to 2-oxazolidinones.
Copper-catalyzed regioselective 1,4-sulfonylcyanation of 1,3-enynes with sulfonyl chlorides and TMSCN
Authors: Lv Yunhe , Han Wanru , Pu Weiya , Xie Jinhui , Wang Axue , Zhang Mengyue , Wang Jin , Lai Junrong
Published: June 2022

A novel and practical copper-catalyzed 1,4-sulfonylcyanation of 1,3-enynes with sulfonyl chlorides and TMSCN has been developed under mild conditions.
Highly stereoselective and enantiodivergent synthesis of cyclopropylphosphonates with engineered carbene transferases
Authors: Ren Xinkun , Chandgude Ajay L. , Carminati Daniela M. , Shen Zhuofan , Khare Sagar D. , Fasan Rudi
Published: June 2022

Two enantiocomplementary myoglobin-based carbene transfer biocatalysts were developed for the synthesis of cyclopropylphosphonate esters with high diastereo- and enantioselectivity and in high yields.
Point-of-care and self-testing for potassium: recent advances
Authors: Hutter Tanya , Collings Thomas S. , Kostova Gratsiela , Karet Frankl Fiona E.
Published: June 2022

The review summarizes recent advances in technologies and devices for point-of-care and self-testing of potassium in venous blood, fingerprick blood, interstitial fluid, sweat, urine, and indirectly using ECG.
Novel system for road traffic optimisation in large cities
Authors: Alkhatib Ahmad A. A. , Abu Maria Khulood , Alzu'bi Shadi , Abu Maria Eman
Published: June 2022

Traffic congestion and road intersection management have become a significant issue, mainly with the highly increasing number of vehicles in cities. There is a common belief from vehicle drivers that installing traffic lights with some consideration of traffic flows will be dominant in traffic movements. This article proposes a novel system for Urban Traffic Control (UTC) with a continuous dynamic environment adaptation to improve traffic flow on large cities' network roads. The proposed system introduces vehicle counting method, lane evaluation of the current status and controlling method considering the effect on the whole traffic network—not just the intersection itself—to provide an efficient traffic scheduling. The main objective of the authors’ system is to reduce traffic jam, by reducing waiting time and trip time for vehicles at intersections. Some indicators and models are introduced in this work to assign traffic flow schedules with minimum traffic congestion and vehicle waiting time. These indicators and models include a traffic jam indicator, vehicle priority and lane weight. A multi‐agent urban traffic control system is proposed as the simulation environment using NetLogo simulator. (A total of 150) Vehicles are generated with random behaviour distributed over 25 intersections for 9 h duration to compare the normal fixed cycle traffic light and the authors’ smart traffic control. Results show a reduction in the total average waiting time of all vehicles for the simulation period by more than (29.98%). Hence, it is more suitable for the complexity of the current traffic condition with minimum changing infrastructure.
Numerical simulation on heat transfer and entropy generation of impingement cooling on boss shaped surface
Authors: ZHANG Lixi , CAO Gaopan , ZHANG Zhengyang
Published: June 2022

Using impingement jet to cool the external cavity of the end wall of the gas turbine guide blade is very effective for prolonging the service life of the gas turbine and ensuring its safety operation. In this paper, the numerical simulation method is used to study the impingement cooling heat transfer performance of the boss shaped surface in the external cavity of the end wall of the gas turbine guide blade, and the entropy generation of the impingement heat transfer process is analyzed. The results show that the average Nusselt number on the impingement target surface and the impingement hole surface increase with the increase of the Reynolds number of the impingement jet. When the Reynolds number is constant, the average Nusselt number of impingement target surface and impingement hole surface decrease with the increase of impingement target distance, but the cooling range on the impingement target surface increases and the heat transfer is more uniform. With the increase of the width of the boss shaped upper surface, the cooling range on the impingement target surface relatively decreases, and the average Nusselt numbers of the impingement target surface decreases and that of the impingement hole surface increases respectively. The heat transfer of the upper surface of the boss is better than that of the lower surface on both sides. The entropy generation in the process of impingement cooling mainly comes from the entropy production caused by viscous dissipation and the entropy flow caused by heat transfer. The entropy production in the flow vortex region is the main reason for the entropy generation. The research conclusions can provide basis and reference for optimizing the structural and operating parameters of boss shaped impingement cavity and improving its impingement heat transfer effect.
A method of brain computer cooperative navigation combined with simultaneous localization and mapping
Authors: XIE Songyun , ZHANG Xiaowei , ZHOU Liuzhi , LIU Xianghui , XIE Xinzhou
Published: June 2022

Introducing human brain intelligence into robot system is an effective means to improve robot's cognition and decision-making ability. Aiming at the problems of human brain fatigue and the need of multi lead information in brain robot control, a brain computer cooperative navigation method combining synchronous localization and mapping (SLAM) is proposed in this paper. Through the steady-state visual evoked potential based on three leads, the image of the target area of interest of human brain is selected, and the brain computer cooperative navigation task is completed by combining SLAM and artificial potential field. The test results show that the average accuracy of the target area image selection method based on steady-state visual evoked potential is 94.17%, which proves that the three leads are effective. On this basis, the brain computer cooperative navigation method combined with SLAM is tested. The results show that the completion rate of navigation task is as high as 92.5%. This method alleviates the fatigue of human brain and reduces the hardware requirements of EEG acquisition.
Research on airworthiness test technology of radiation emission in civil aircraft flight control electronic system
Authors: LU Kuan , LI Aijun , LI Linxiao , WANG Tianbo , WANG Jianyuan
Published: June 2022

It is the first time that domestic civil large aircraft has been developed, which lacks the technical experience of airborne system-level airworthiness qualification, and the research of radiation emission at home and abroad is mainly based on simulation evaluation, while the simulation results are used only as a reference in the airworthiness qualification process and cannot be used as evidence of conformity. And there is little airworthiness test experience on complex system-level. In this paper, taking civil aircraft flight control electronic system as an example, translate airworthiness compliance requirements into engineering requirements, analyze the complexity characteristics of civil aircraft flight control system, build flight control electronic system level radiation emission test system, and improve the system level airworthiness qualification test and optimization process, providing experience for the airworthiness qualification of civil aircraft complex system. The results show that the radiation emission of flight control electronic system is greatly affected by the system environment, and it is necessary to consider the influence of test setup layout and show the system compliance to the RTCA/DO-160G requirements.
A reconfigurable processor for mix-precision CNNs on FPGA
Authors: CHANG Libo , ZHANG Shengbing
Published: June 2022

To solve the problem of low computing efficiency of existing accelerators for convolutional neural network (CNNs), which caused by the inability to adapt to the characteristics of computing mode and caching for the mixed-precision quantized CNNs model, we propose a reconfigurable CNN processor in this paper, which consists of the reconfigurable adaptable computing unit, flexible on-chip cache unit and macro-instruction set. The multi-core CNN processor can be reconstructed according to the structure of CNN models and constraints of reconfigurable resources, to improve the utilization of computing resources. The elastic on-chip buffer and the data access approach by dynamically configuring an address to better utilization of on-chip memory. Then, the macroinstruction set architecture (mISA) can fully express the characteristics of the mixed-precision CNN models and reconfigurable processors, to reduce the complexity of mapping CNNs with different network structures and computing modes to reconfigurable the CNNs processors. For the well-known CNNs-VGG16 and ResNet-50, the proposed CNN processor has been implemented using Ultra96-V2 and ZCU102 FPGA, showing the throughput of 216.6 GOPS, and 214 GOPS, the computing efficiency of 0.63 GOPS/DSP and 0.64 GOPS/DSP on Ultra96-V2, respectively, achieving a better efficiency than the CNN accelerator based on fixed bit-width. Meanwhile, for ResNet-50, the throughput and the computing efficiency are up to 931.8 GOPS, 0.40 GOPS/DSP on ZCU102, respectively. In addition, these achieve up to 55.4% higher throughput than state-of-the-art CNN accelerators.
Exploring sub-strong scattering source of canopy of fighter with radar stealth technology
Authors: ZHOU Tao , ZHOU Shenglin , CAI Sanjun , YANG Bo , YUE Yingzhang
Published: June 2022

The canopy of a fighter is the main source of electromagnetic scattering, and the achievement of its radar stealth is one of key technologies for developing a stealth fighter. The scattering sources mainly include the scattering in the cavity of the canopy (strong scattering source) and the local structural scattering (sub-strong scattering source). To satisfy the high stealth requirements, it is necessary to reduce the RCS of the sub-strong scattering source of the canopy. This paper studies the sub-strong scattering source of the canopy of a stealth fighter and proposes the canopy's sub-strong scattering source reduction and control measure by applying the basic radar stealth technology, the MLFMM and the RCS test.
Study on experiment platform for flight control system of general aircraft
Authors: DAI Guicheng , FAN Yanming , LI Donghui , MA Hongtu , MEI Li
Published: June 2022

Currently, the development of general aircraft is a new hotspot in the field of domestic civil aviation. But the development of general aircraft R & D is relatively lag comparing to the military and commercial transport aircraft, and lack of validation and experiment platform for flight control system. Based on the necessity, basic design principles of the experiment platform and the test items of general aircraft, a design scheme of the general platform was proposed. The scheme was composed of the human-aircraft interface subsystem, hardware construction environment subsystem, aircraft motion simulation subsystem, signal acquisition/processing subsystem and so on. At the same time, the flight simulation and test of man-in-loop are realized. This platform is used to test the flight control system characteristics of an electric general aircraft. The test results demonstrated that the platform is stable and reliable, and can resolve the problem of general aircraft fight control system testing effectively.
Underwater object detection algorithm based on channel attention and feature fusion
Authors: ZHANG Yan , LI Xingshan , SUN Yemei , LIU Shudong
Published: June 2022

Due to the color deviation, low contrast and fuzzy object in underwater optical images, there are some problems in underwater object detection, such as missed detection and false detection. In order to solve the above-mentioned problems, an underwater object detection algorithm is proposed based on the channel attention and feature fusion for underwater optical images. The excitation residual module is designed based on the channel attention, and the forward propagation feature information is adaptively allocated weights to highlight the salience of different channel feature maps, which improves the network ability to extract high-frequency information from the underwater images. The multi-scale feature fusion module is designed to add a large scale feature map for object detection, which improves the detection performance of the network for small size objects by using its corresponding small size receptive field, and further improves the detection accuracy of the network for different size objects in the underwater environment. To improve the generalization performance of the network to the underwater environment, the data augmentation method based on the stitching and fusion is designed to simulate the overlap, occlusion and blurring of underwater objects, which improves the adaptability of the network to the underwater environment. Through experiments on the public dataset URPC, the algorithm in this paper improves the mean average precision by 5.42%, 3.20% and 0.9% compared with YOLOv3, YOLOv4 and YOLOv5, respectively, effectively improving the missed and false detection of objects of different sizes in complex underwater environments.