bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of Venusian Wrinkle Ridge Morphometry Using Stereo‐Derived Topography: A Case Study From Southern Eistla Regio
Authors: Bethell E. M. , Ernst R. E. , Samson C. 
Published: April 2022

AbstractWe present an analysis of 503 topographic profiles taken across 40 ENE‐WSW trending wrinkle ridges from Southern Eistla Regio, Venus, using stereo‐derived topography. We find that their average widths and heights are on the order of 10 km and 100 m, respectively. While the majority of the wrinkle ridges are asymmetric and display vergence to the southeast, some are quasi‐symmetric, possibly representing pop‐up structures, and possess multiple peaks along the backslope, potentially indicating the presence of secondary backthrust faults. Fault geometry modeling in which the average observed wrinkle ridge topographic profile is matched to the calculated surface deformation while varying various faulting parameters indicates that the wrinkle ridges studied have dips of 30°, penetrate to depths of 5 km or less, are blind and reach to within 2 km of the surface, have accommodated approximately 200 m of slip, and possess a planar geometry. These results imply that the wrinkle ridges formed through a thin‐skinned deformation style. The spacing and distribution of the wrinkle ridges at a regional scale displays a clear relationship between wrinkle ridge deformation and lithospheric properties. We therefore conclude that the distribution of wrinkle ridges in the study area is a direct reflection of the regional strain which, in turn, is a result of mantle dynamics coupled with lithospheric thickness. The accumulation of contractional deformation expressed as wrinkle ridges appears to be the result of mantle downwelling along the peripheries of Eistla Regio.
Acoustofluidics for simultaneous nanoparticle-based drug loading and exosome encapsulation
Authors: Wang Zeyu , Rich Joseph , Hao Nanjing , Gu Yuyang , Chen Chuyi , Yang Shujie , Zhang Peiran , Huang Tony Jun 
Published: April 2022

AbstractNanocarrier and exosome encapsulation has been found to significantly increase the efficacy of targeted drug delivery while also minimizing unwanted side effects. However, the development of exosome-encapsulated drug nanocarriers is limited by low drug loading efficiencies and/or complex, time-consuming drug loading processes. Herein, we have developed an acoustofluidic device that simultaneously performs both drug loading and exosome encapsulation. By synergistically leveraging the acoustic radiation force, acoustic microstreaming, and shear stresses in a rotating droplet, the concentration, and fusion of exosomes, drugs, and porous silica nanoparticles is achieved. The final product consists of drug-loaded silica nanocarriers that are encased within an exosomal membrane. The drug loading efficiency is significantly improved, with nearly 30% of the free drug (e.g., doxorubicin) molecules loaded into the nanocarriers. Furthermore, this acoustofluidic drug loading system circumvents the need for complex chemical modification, allowing drug loading and encapsulation to be completed within a matter of minutes. These exosome-encapsulated nanocarriers exhibit excellent efficiency in intracellular transport and are capable of significantly inhibiting tumor cell proliferation. By utilizing physical forces to rapidly generate hybrid nanocarriers, this acoustofluidic drug loading platform wields the potential to significantly impact innovation in both drug delivery research and applications.
The relationship between immune and cognitive dysfunction in mood and psychotic disorder: a systematic review and a meta-analysis
Authors: Morrens M. , Overloop C. , Coppens V. , Loots E. , Van Den Noortgate M. , Vandenameele S. , Leboyer M. , De Picker L. 
Published: April 2022

Abstract
Background
In psychotic and mood disorders, immune alterations are hypothesized to underlie cognitive symptoms, as they have been associated with elevated blood levels of inflammatory cytokines, kynurenine metabolites, and markers of microglial activation. The current meta-analysis synthesizes all available clinical evidence on the associations between immunomarkers (IMs) and cognition in these psychiatric illnesses.

Methods
Pubmed, Web of Science, and Psycinfo were searched for peer-reviewed studies on schizophrenia spectrum disorder (SZ), bipolar disorder (BD), or major depressive disorder (MDD) including an association analysis between at least one baseline neuropsychological outcome measure (NP) and one IM (PROSPERO ID:CRD42021278371). Quality assessment was performed using BIOCROSS. Correlation meta-analyses, and random effect models, were conducted in Comprehensive Meta-Analysis version 3 investigating the association between eight cognitive domains and pro-inflammatory and anti-inflammatory indices (PII and AII) as well as individual IM.

Results
Seventy-five studies (n = 29,104) revealed global cognitive performance (GCP) to be very weakly associated to PII (r = −0.076; p = 0.003; I2 = 77.4) or AII (r = 0.067; p = 0.334; I2 = 38.0) in the combined patient sample. Very weak associations between blood–based immune markers and global or domain-specific GCP were found, either combined or stratified by diagnostic subgroup (GCP x PII: SZ: r = −0.036, p = 0.370, I2 = 70.4; BD: r = −0.095, p = 0.013, I2 = 44.0; MDD: r = −0.133, p = 0.040, I2 = 83.5). We found evidence of publication bias.

Discussion
There is evidence of only a weak association between blood-based immune markers and cognition in mood and psychotic disorders. Significant publication and reporting biases were observed and most likely underlie the inflation of such associations in individual studies.
MyD88 in hepatic stellate cells enhances liver fibrosis via promoting macrophage M1 polarization
Authors: Zhang Jie , Liu Yu , Chen Haiqiang , Yuan Qi , Wang Jinyan , Niu Meng , Hou Lingling , Gu Jianchun , Zhang Jinhua 
Published: April 2022

AbstractDuring liver fibrosis, quiescent HSCs (qHSCs) are activated to become activated HSCs (aHSCs)/myofibroblasts. The signal adapter MyD88, an essential component of TLR signaling, plays an important role in liver fibrosis. However, far less is known about the specific effects of MyD88 signaling in both qHSCs and aHSCs in the progress of liver fibrosis. Here, we used a CCl4-induced mouse fibrosis model in which MyD88 was selectively depleted in qHSCs (GFAPMyD88−/− mice) or aHSCs (α-SMAMyD88−/− mice). MyD88 deficiency in qHSCs or aHSCs attenuated liver fibrosis in mice and inhibited α-SMA-positive cell activation. Inhibition of MyD88 in HSCs decreased α-SMA and collagen I levels, inflammatory cell infiltration, and pro-inflammatory gene expression. Furthermore, MyD88 signaling in HSCs increased the secretion of CXCL10, which promoted macrophage M1 polarization through CXCR3, leading to activation of the JAK/STAT1 pathway. Inhibition of CXCL10 attenuated macrophage M1 polarization and reduced liver fibrosis. Thus, MyD88 signaling in HSCs crucially contributes to liver fibrosis and provides a promising therapeutic target for the prevention and treatment of liver fibrosis.
Defective hematopoietic differentiation of immune aplastic anemia patient-derived iPSCs
Authors: Tellechea Maria Florencia , Donaires Flávia S. , de Carvalho Vinícius S. , Santana Bárbara A. , da Silva Fernanda B. , Tristão Raissa S. , Moreira Lílian F. , de Souza Aline F. , Armenteros Yordanka M. , Pereira Lygia V. , Calado Rodrigo T. 
Published: April 2022

AbstractIn acquired immune aplastic anemia (AA), pathogenic cytotoxic Th1 cells are activated and expanded, driving an immune response against the hematopoietic stem and progenitor cells (HSPCs) that provokes cell depletion and causes bone marrow failure. However, additional HSPC defects may contribute to hematopoietic failure, reflecting on disease outcomes and response to immunosuppression. Here we derived induced pluripotent stem cells (iPSCs) from peripheral blood (PB) erythroblasts obtained from patients diagnosed with immune AA using non-integrating plasmids to model the disease. Erythroblasts were harvested after hematologic response to immunosuppression was achieved. Patients were screened for germline pathogenic variants in bone marrow failure-related genes and no variant was identified. Reprogramming was equally successful for erythroblasts collected from the three immune AA patients and the three healthy subjects. However, the hematopoietic differentiation potential of AA-iPSCs was significantly reduced both quantitatively and qualitatively as compared to healthy-iPSCs, reliably recapitulating disease: differentiation appeared to be more severely affected in cells from the two patients with partial response as compared to the one patient with complete response. Telomere elongation and the telomerase machinery were preserved during reprogramming and differentiation in all AA-iPSCs. Our results indicate that iPSCs are a reliable platform to model immune AA and recapitulate clinical phenotypes. We propose that the immune attack may cause specific epigenetic changes in the HSPCs that limit adequate proliferation and differentiation.
A reversibly gated protein-transporting membrane channel made of DNA
Authors: Dey Swarup , Dorey Adam , Abraham Leeza , Xing Yongzheng , Zhang Irene , Zhang Fei , Howorka Stefan , Yan Hao 
Published: April 2022

AbstractControlled transport of biomolecules across lipid bilayer membranes is of profound significance in biological processes. In cells, cargo exchange is mediated by dedicated channels that respond to triggers, undergo a nanomechanical change to reversibly open, and thus regulate cargo flux. Replicating these processes with simple yet programmable chemical means is of fundamental scientific interest. Artificial systems that go beyond nature’s remit in transport control and cargo are also of considerable interest for biotechnological applications but challenging to build. Here, we describe a synthetic channel that allows precisely timed, stimulus-controlled transport of folded and functional proteins across bilayer membranes. The channel is made via DNA nanotechnology design principles and features a 416 nm2opening cross-section and a nanomechanical lid which can be controllably closed and re-opened via a lock-and-key mechanism. We envision that the functional DNA device may be used in highly sensitive biosensing, drug delivery of proteins, and the creation of artificial cell networks.
Implementing in-situ self-organizing maps with memristor crossbar arrays for data mining and optimization
Authors: Wang Rui , Shi Tuo , Zhang Xumeng , Wei Jinsong , Lu Jian , Zhu Jiaxue , Wu Zuheng , Liu Qi , Liu Ming 
Published: April 2022

AbstractA self-organizing map (SOM) is a powerful unsupervised learning neural network for analyzing high-dimensional data in various applications. However, hardware implementation of SOM is challenging because of the complexity in calculating the similarities and determining neighborhoods. We experimentally demonstrated a memristor-based SOM based on Ta/TaOx/Pt 1T1R chips for the first time, which has advantages in computing speed, throughput, and energy efficiency compared with the CMOS digital counterpart, by utilizing the topological structure of the array and physical laws for computing without complicated circuits. We employed additional rows in the crossbar arrays and identified the best matching units by directly calculating the similarities between the input vectors and the weight matrix in the hardware. Using the memristor-based SOM, we demonstrated data clustering, image processing and solved the traveling salesman problem with much-improved energy efficiency and computing throughput. The physical implementation of SOM in memristor crossbar arrays extends the capability of memristor-based neuromorphic computing systems in machine learning and artificial intelligence.
A theory of cortical map formation in the visual brain
Authors: Najafian Sohrab , Koch Erin , Teh Kai Lun , Jin Jianzhong , Rahimi-Nasrabadi Hamed , Zaidi Qasim , Kremkow Jens , Alonso Jose-Manuel 
Published: April 2022

AbstractThe cerebral cortex receives multiple afferents from the thalamus that segregate by stimulus modality forming cortical maps for each sense. In vision, the primary visual cortex maps the multiple dimensions of the visual stimulus in patterns that vary across species for reasons unknown. Here we introduce a general theory of cortical map formation, which proposes that map diversity emerges from species variations in the thalamic afferent density sampling sensory space. In the theory, increasing afferent sampling density enlarges the cortical domains representing the same visual point, allowing the segregation of afferents and cortical targets by multiple stimulus dimensions. We illustrate the theory with an afferent-density model that accurately replicates the maps of different species through afferent segregation followed by thalamocortical convergence pruned by visual experience. Because thalamocortical pathways use similar mechanisms for axon segregation and pruning, the theory may extend to other sensory areas of the mammalian brain.
Allogeneic TCRαβ deficient CAR T-cells targeting CD123 in acute myeloid leukemia
Authors: Sugita Mayumi , Galetto Roman , Zong Hongliang , Ewing-Crystal Nathan , Trujillo-Alonso Vicenta , Mencia-Trinchant Nuria , Yip Winnie , Filipe Stephanie , Lebuhotel Celine , Gouble Agnès , Hassane Duane C. , Smith Julianne , Roboz Gail J. , Guzman Monica L. 
Published: April 2022

AbstractAcute myeloid leukemia (AML) is a disease with high incidence of relapse that is originated and maintained from leukemia stem cells (LSCs). Hematopoietic stem cells can be distinguished from LSCs by an array of cell surface antigens such as CD123, thus a candidate to eliminate LSCs using a variety of approaches, including CAR T cells. Here, we evaluate the potential of allogeneic gene-edited CAR T cells targeting CD123 to eliminate LSCs (UCART123). UCART123 cells are TCRαβneg T cells generated from healthy donors using TALEN® gene-editing technology, decreasing the likelihood of graft vs host disease. As safety feature, cells express RQR8 to allow elimination with Rituximab. UCART123 effectively eliminates AML cells in vitro and in vivo with significant benefits in overall survival of AML-patient derived xenograft mice. Furthermore, UCART123 preferentially target AML over normal cells with modest toxicity to normal hematopoietic stem/progenitor cells. Together these results suggest that UCART123 represents an off-the shelf therapeutic approach for AML.
Targeting CD123 in blastic plasmacytoid dendritic cell neoplasm using allogeneic anti-CD123 CAR T cells
Authors: Cai Tianyu , Gouble Agnès , Black Kathryn L. , Skwarska Anna , Naqvi Ammar S. , Taylor Deanne , Zhao Ming , Yuan Qi , Sugita Mayumi , Zhang Qi , Galetto Roman , Filipe Stéphanie , Cavazos Antonio , Han Lina , Kuruvilla Vinitha , Ma Helen , Weng Connie , Liu Chang-Gong , Liu Xiuping , Konoplev Sergej , Gu Jun , Tang Guilin , Su Xiaoping , Al-Atrash Gheath , Ciurea Stefan , Neelapu Sattva S. , Lane Andrew A. , Kantarjian Hagop , Guzman Monica L. , Pemmaraju Naveen , Smith Julianne , Thomas-Tikhonenko Andrei , Konopleva Marina 
Published: April 2022

AbstractBlastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy with poor outcomes with conventional therapy. Nearly 100% of BPDCNs overexpress interleukin 3 receptor subunit alpha (CD123). Given that CD123 is differentially expressed on the surface of BPDCN cells, it has emerged as an attractive therapeutic target. UCART123 is an investigational product consisting of allogeneic T cells expressing an anti-CD123 chimeric antigen receptor (CAR), edited with TALEN® nucleases. In this study, we examine the antitumor activity of UCART123 in preclinical models of BPDCN. We report that UCART123 have selective antitumor activity against CD123-positive primary BPDCN samples (while sparing normal hematopoietic progenitor cells) in the in vitro cytotoxicity and T cell degranulation assays; supported by the increased secretion of IFNγ by UCART123 cells when cultured in the presence of BPDCN cells. UCART123 eradicate BPDCN and result in long-term disease-free survival in a subset of primary patient-derived BPDCN xenograft mouse models. One potential challenge of CD123 targeting therapies is the loss of CD123 antigen through diverse genetic mechanisms, an event observed in one of three BPDCN PDX studied. In summary, these results provide a preclinical proof-of-principle that allogeneic UCART123 cells have potent anti-BPDCN activity.
Vertically stacked, low-voltage organic ternary logic circuits including nonvolatile floating-gate memory transistors
Authors: Choi Junhwan , Lee Changhyeon , Lee Chungryeol , Park Hongkeun , Lee Seung Min , Kim Chang-Hyun , Yoo Hocheon , Im Sung Gap 
Published: April 2022

AbstractMulti-valued logic (MVL) circuits based on heterojunction transistor (HTR) have emerged as an effective strategy for high-density information processing without increasing the circuit complexity. Herein, an organic ternary logic inverter (T-inverter) is demonstrated, where a nonvolatile floating-gate flash memory is employed to control the channel conductance systematically, thus realizing the stabilized T-inverter operation. The 3-dimensional (3D) T-inverter is fabricated in a vertically stacked form based on all-dry processes, which enables the high-density integration with high device uniformity. In the flash memory, ultrathin polymer dielectrics are utilized to reduce the programming/erasing voltage as well as operating voltage. With the optimum programming state, the 3D T-inverter fulfills all the important requirements such as full-swing operation, optimum intermediate logic value (~VDD/2), high DC gain exceeding 20 V/V as well as low-voltage operation (< 5 V). The organic flash memory exhibits long retention characteristics (current change less than 10% after 104 s), leading to the long-term stability of the 3D T-inverter. We believe the 3D T-inverter employing flash memory developed in this study can provide a useful insight to achieve high-performance MVL circuits.
Stopping molecular rotation using coherent ultra-low-energy magnetic manipulations
Authors: Chadwick Helen , Somers Mark F. , Stewart Aisling C. , Alkoby Yosef , Carter Thomas J. D. , Butkovicova Dagmar , Alexandrowicz Gil 
Published: April 2022

AbstractRotational motion lies at the heart of intermolecular, molecule-surface chemistry and cold molecule science, motivating the development of methods to excite and de-excite rotations. Existing schemes involve perturbing the molecules with photons or electrons which supply or remove energy comparable to the rotational level spacing. Here, we study the possibility of de-exciting the molecular rotation of a D2 molecule, from J = 2 to the non-rotating J = 0 state, without using an energy-matched perturbation. We show that passing the beam through a 1 m long magnetic field, which splits the rotational projection states by only 10−12 eV, can change the probability that a molecule-surface collision will stop a molecule from rotating and lose rotational energy which is 9 orders larger than that of the magnetic manipulation. Calculations confirm that different rotational orientations have different de-excitation probabilities but underestimate rotational flips (∆mJ$$\ne$$
≠
0), highlighting the importance of the results as a sensitive benchmark for further developing theoretical models of molecule-surface interactions.
Deficiency in coatomer complex I causes aberrant activation of STING signalling
Authors: Steiner Annemarie , Hrovat-Schaale Katja , Prigione Ignazia , Yu Chien-Hsiung , Laohamonthonkul Pawat , Harapas Cassandra R. , Low Ronnie Ren Jie , De Nardo Dominic , Dagley Laura F. , Mlodzianoski Michael J. , Rogers Kelly L. , Zillinger Thomas , Hartmann Gunther , Gantier Michael P. , Gattorno Marco , Geyer Matthias , Volpi Stefano , Davidson Sophia , Masters Seth L. 
Published: April 2022

AbstractCoatomer complex I (COPI) mediates retrograde vesicular trafficking from Golgi to the endoplasmic reticulum (ER) and within Golgi compartments. Deficiency in subunit alpha causes COPA syndrome and is associated with type I IFN signalling, although the upstream innate immune sensor involved was unknown. Using in vitro models we find aberrant activation of the STING pathway due to deficient retrograde but probably not intra-Golgi transport. Further we find the upstream cytosolic DNA sensor cGAS as essentially required to drive type I IFN signalling. Genetic deletion of COPI subunits COPG1 or COPD similarly induces type I IFN activation in vitro, which suggests that inflammatory diseases associated with mutations in other COPI subunit genes may exist. Finally, we demonstrate that inflammation in COPA syndrome patient peripheral blood mononuclear cells and COPI-deficient cell lines is ameliorated by treatment with the small molecule STING inhibitor H-151, suggesting targeted inhibition of the cGAS/STING pathway as a promising therapeutic approach.
Switchable bifunctional molecular recognition in water using a pH-responsive Endo-functionalized cavity
Authors: Wang Xiaoping , Quan Mao , Yao Huan , Pang Xin-Yu , Ke Hua , Jiang Wei 
Published: April 2022

AbstractThe construction of water-soluble synthetic hosts with a stimuli-responsive endo-functionalized cavity is challenging. These hosts feature a switchable cavity and may bring new properties to the fields of self-assembly, molecular machines, and biomedical sciences. Herein, we report a pair of water-soluble naphthotubes with a pH-responsive endo-functionalized cavity. The inward-directing secondary amine group of the hosts can be protonated and deprotonated. Thus, the hosts have different cavity features at the two states and show drastically different binding preference and selectivity in water. We reveal that the binding difference of the two host states is originated from the differences in charge repulsion, hydrogen bonding and the hydrophobic effects. Moreover, the guest binding can be easily switched in a ternary mixture with two guest molecules by adjusting the pH value of the solution. These pH-responsive hosts may be used for the construction of smart self-assembly systems and water-soluble molecular machines.