bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neither Perfect Nor Ideal: Palladio’s Villa Rotonda
Authors: Hopkins Andrew 
Published: November 2022

ABSTRACTThis article demonstrates that the most celebrated building designed by Andrea Palladio, widely known as the Villa Rotonda and begun around 1566, was left only partially constructed at the time of the architect’s death in 1580 and that, as a villa design, it was neither perfect nor ideal. Drawing on detailed records of the construction work carried out in the 1590s, the article shows that much of the villa was constructed or altered after Palladio died, in significant part so as to deal with practical difficulties and deficiencies inherent in the design originally published in Palladio’s treatise. Scholars in general have come to recognise that the Villa Rotonda is something of a palimpsest. However, it has not been properly understood that the building was largely constructed not as an adjusted scheme devised by Palladio, but rather as a strategically revised concept for a villa developed after Palladio’s time by Vincenzo Scamozzi. This preserved something of the original scheme as a hilltop belvedere — especially its outward appearance as a domed and isolated block with four near-identical porticoes — but it adapted what had been built, which was far from complete, to a much more practical vision of the requirements of rural life. What was built during this later period then remained intact until the late eighteenth century.
The role of the clinical pharmacist in antimicrobial stewardship in Asia: A review
Authors: Jantarathaneewat Kittiya , Camins Bernard , Apisarnthanarak Anucha 
Published: November 2022

Abstract
Clinical pharmacist-driven antimicrobial stewardship programs (ASPs) have been successfully implemented. Although relevant guidance and several studies suggest that clinical pharmacists be integrated into the current ASP team model, barriers still exist in Asia, primarily due to lack of dedicated personnel and lack of career advancement. We review the effectiveness and the ideal role of clinical pharmacist among ASPs in Asia. Several studies conducted in Asia have shown the effectiveness of pharmacist-led ASP interventions in hospitals and other healthcare settings. However, opportunities to expand the role of clinical pharmacists in ASPs in Asia exist in the implementation of rapid diagnostic test and drug allergies.
Dam Impacts on Seasonality of Water and Sediment Transport in Intensively Managed River Basins: A Case Study of the Yangtze River
Authors: Tian Q. , Xu K. H. , Wang Y. P. , Liang C. J. 
Published: November 2022

AbstractExtensive studies have been performed on water and sediment transport of the Yangtze River in recent decades, but very few studies were focused on seasonal and daily variations. After the construction of Three Gorges Dam (TGD) in 2003, several key cascade dams were built on the Yangtze upstream. Annual, monthly, and daily data were used to study the seasonality change on water level, water discharge, and sediment load in response to multiple reservoir impoundments. TGD impacted the water level inside the reservoir greatly by shifting the peak water level from summer to winter and made the hydrograph more asymmetrical. In contrast, minor changes in water levels (<2 m) occurred at stations downstream of the TGD mainly due to channel incision. Downstream of TGD at Yichang station, annual hydrograph was flattened slightly: water discharge in the dry season increased 49% whereas that of flood season decreased 14% from 1956–2002 to 2013–2017. Mean annual water discharge downstream of the TGD was slightly impacted because the impounded water was <5% of annual inflow of the reservoir. Comparing with the Yangtze, the annual hydrographs of other intensively managed rivers like the Yellow, Missouri, and Colorado have been flattened more effectively by reservoir impoundments. The sediment rating curves at Yichang and Hankou changed from an oval‐like shape before 2013 to two overlapping and flattened lines in 2013–2017. This shift indicates that the rising and falling limbs of the hydrograph experienced similar sediment concentrations in 2013–2017 and suggests a less obvious hysteresis effect. Over 50% of the sediment load observed at the seaward‐most Datong station was contributed by the large tributaries in the upper reach, like Jinsha and Jialing rivers, before 2003. The channel scour downstream of TGD contributed 49%–64% of the Datong sediment load after 2003.
Compact Shortened V‐Band Conical Dielectric Core Horns Corrected by Lenses
Authors: Gil J. M. 
Published: November 2022

AbstractA procedure of designing ultra‐short conical horns corrected by lenses, is boarded at this work. The method takes advantages of the axisymmetric character of the conical horns to project the problem to a bidimensional mesh, reducing the computational time and making easy the optimization of the device. This approach is not used for most popular commercial codes which employ a 3D analysis of the whole antenna. Horn antennas exhibit some remarkable radiation characteristics as they are high directivity, low crosspolar level and symmetric patterns with low return losses on a reasonable bandwidth. The price to pay is handle devices very long and weighed, so it is demanding to find lines of design to shorten and make compact horns to be incorporated to the current communication systems. In this work, we show the advantages to use a double convex lens together with a dielectric core, added to the horn, to achieve a compact and shortened horn maintaining a good performance. Conical horns, of a size as small as one wavelength, can be achieved. To reach such shortening, a double convex lens and a dielectric core must be added to the antenna. The parameters of the final prototype, at 60 GHz, are the following: Length: ≈λ, Directivity = 20 dBi, Cross polar Peak = −19.1 dB, Beam width on copular plane = 18.3°, Side Lobe Levels lower than −20 dB (both H and E plane), Return losses = −30.7 dB, and presenting an smooth frequency behavior on a wide bandwidth.
LINC01468 drives NAFLD-HCC progression through CUL4A-linked degradation of SHIP2
Authors: Wang Hongquan , Wang Yan , Lai Shihui , Zhao Liang , Liu Wenhui , Liu Shiqian , Chen Haiqiang , Wang Jinhua , Du Guanhua , Tang Bo 
Published: November 2022

AbstractAccumulating evidence suggests that long noncoding RNAs (lncRNAs) are deregulated in hepatocellular carcinoma (HCC) and play a role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). However, the current understanding of the role of lncRNAs in NAFLD-associated HCC is limited. In this study, transcriptomic profiling analysis of three paired human liver samples from patients with NAFLD-driven HCC and adjacent samples showed that LINC01468 expression was significantly upregulated. In vitro and in vivo gain- and loss-of-function experiments showed that LINC01468 promotes the proliferation of HCC cells through lipogenesis. Mechanistically, LINC01468 binds SHIP2 and promotes cullin 4 A (CUL4A)-linked ubiquitin degradation, thereby activating the PI3K/AKT/mTOR signaling pathway, resulting in the promotion of de novo lipid biosynthesis and HCC progression. Importantly, the SHIP2 inhibitor reversed the sorafenib resistance induced by LINC01468 overexpression. Moreover, ALKBH5-mediated N6-methyladenosine (m6A) modification led to stabilization and upregulation of LINC01468 RNA. Taken together, the findings indicated a novel mechanism by which LINC01468-mediated lipogenesis promotes HCC progression through CUL4A-linked degradation of SHIP2. LINC01468 acts as a driver of HCC progression from NAFLD, highlights the potential of the LINC01468-SHIP2 axis as a therapeutic target for HCC.
Robust replication initiation from coupled homeostatic mechanisms
Authors: Berger Mareike , Wolde Pieter Rein ten 
Published: November 2022

AbstractThe bacterium Escherichia coli initiates replication once per cell cycle at a precise volume per origin and adds an on average constant volume between successive initiation events, independent of the initiation size. Yet, a molecular model that can explain these observations has been lacking. Experiments indicate that E. coli controls replication initiation via titration and activation of the initiator protein DnaA. Here, we study by mathematical modelling how these two mechanisms interact to generate robust replication-initiation cycles. We first show that a mechanism solely based on titration generates stable replication cycles at low growth rates, but inevitably causes premature reinitiation events at higher growth rates. In this regime, the DnaA activation switch becomes essential for stable replication initiation. Conversely, while the activation switch alone yields robust rhythms at high growth rates, titration can strongly enhance the stability of the switch at low growth rates. Our analysis thus predicts that both mechanisms together drive robust replication cycles at all growth rates. In addition, it reveals how an origin-density sensor yields adder correlations.
Neural circuit dynamics of drug-context associative learning in the mouse hippocampus
Authors: Sun Yanjun , Giocomo Lisa M. 
Published: November 2022

AbstractThe environmental context associated with previous drug consumption is a potent trigger for drug relapse. However, the mechanism by which neural representations of context are modified to incorporate information associated with drugs of abuse remains unknown. Using longitudinal calcium imaging in freely behaving mice, we find that unlike the associative learning of natural reward, drug-context associations for psychostimulants and opioids are encoded in a specific subset of hippocampal neurons. After drug conditioning, these neurons weakened their spatial coding for the non-drug paired context, resulting in an orthogonal representation for the drug versus non-drug context that was predictive of drug-seeking behavior. Furthermore, these neurons were selected based on drug-spatial experience and were exclusively tuned to animals’ allocentric position. Together, this work reveals how drugs of abuse alter the hippocampal circuit to encode drug-context associations and points to the possibility of targeting drug-associated memory in the hippocampus.
Connecting multiple microenvironment proteomes uncovers the biology in head and neck cancer
Authors: Busso-Lopes Ariane F. , Neves Leandro X. , Câmara Guilherme A. , Granato Daniela C. , Pretti Marco Antônio M. , Heberle Henry , Patroni Fábio M. S. , Sá Jamile , Yokoo Sami , Rivera César , Domingues Romênia R. , Normando Ana Gabriela C. , De Rossi Tatiane , Mello Barbara P. , Galdino Nayane A. L. , Pauletti Bianca A. , Lacerda Pammela A. , Rodrigues André Afonso N. , Casarim André Luis M. , de Lima-Souza Reydson A. , Damas Ingrid I. , Mariano Fernanda V. , Gollob Kenneth J. , Medina Tiago S. , Cervigne Nilva K. , Prado-Ribeiro Ana Carolina , Brandão Thaís Bianca , Villa Luisa L. , Uno Miyuki , Boroni Mariana , Kowalski Luiz Paulo , González-Arriagada Wilfredo Alejandro , Paes Leme Adriana F. 
Published: November 2022

AbstractThe poor prognosis of head and neck cancer (HNC) is associated with metastasis within the lymph nodes (LNs). Herein, the proteome of 140 multisite samples from a 59-HNC patient cohort, including primary and matched LN-negative or -positive tissues, saliva, and blood cells, reveals insights into the biology and potential metastasis biomarkers that may assist in clinical decision-making. Protein profiles are strictly associated with immune modulation across datasets, and this provides the basis for investigating immune markers associated with metastasis. The proteome of LN metastatic cells recapitulates the proteome of the primary tumor sites. Conversely, the LN microenvironment proteome highlights the candidate prognostic markers. By integrating prioritized peptide, protein, and transcript levels with machine learning models, we identify nodal metastasis signatures in blood and saliva. We present a proteomic characterization wiring multiple sites in HNC, thus providing a promising basis for understanding tumoral biology and identifying metastasis-associated signatures.
Direct in situ photolithography of perovskite quantum dots based on photocatalysis of lead bromide complexes
Authors: Zhang Pingping , Yang Gaoling , Li Fei , Shi Jianbing , Zhong Haizheng 
Published: November 2022

AbstractPhotolithography has shown great potential in patterning solution-processed nanomaterials for integration into advanced optoelectronic devices. However, photolithography of perovskite quantum dots (PQDs) has so far been hindered by the incompatibility of perovskite with traditional optical lithography processes where lots of solvents and high-energy ultraviolet (UV) light exposure are required. Herein, we report a direct in situ photolithography technique to pattern PQDs based on the photopolymerization catalyzed by lead bromide complexes. By combining direct photolithography with in situ fabrication of PQDs, this method allows to directly photolithograph perovskite precursors, avoiding the complicated lift-off processes and the destruction of PQDs by solvents or high-energy UV light, as PQDs are produced after lithography exposure. We further demonstrate that the thiol-ene free-radical photopolymerization is catalyzed by lead bromide complexes in the perovskite precursor solution, while no external initiators or catalysts are needed. Using direct in situ photolithography, PQD patterns with high resolution up to 2450 pixels per inch (PPI), excellent fluorescence uniformity, and good stability, are successfully demonstrated. This work opens an avenue for non-destructive direct photolithography of high-efficiency light-emitting PQDs, and potentially expands their application in various integrated optoelectronic devices.
Boosting CO hydrogenation towards C2+ hydrocarbons over interfacial TiO2−x/Ni catalysts
Authors: Xu Ming , Qin Xuetao , Xu Yao , Zhang Xiaochen , Zheng Lirong , Liu Jin-Xun , Wang Meng , Liu Xi , Ma Ding 
Published: November 2022

AbstractConsiderable attention has been drawn to tune the geometric and electronic structure of interfacial catalysts via modulating strong metal-support interactions (SMSI). Herein, we report the construction of a series of TiO2−x/Ni catalysts, where disordered TiO2−x overlayers immobilized onto the surface of Ni nanoparticles (~20 nm) are successfully engineered with SMSI effect. The optimal TiO2−x/Ni catalyst shows a CO conversion of ~19.8% in Fischer–Tropsch synthesis (FTS) process under atmospheric pressure at 220 °C. More importantly, ~64.6% of the product is C2+ paraffins, which is in sharp contrast to the result of the conventional Ni catalyst with the main product being methane. A combination study of advanced electron microscopy, multiple in-situ spectroscopic characterizations, and density functional theory calculations indicates the presence of Niδ−/TiO2−x interfacial sites, which could bind carbon atom strongly, inhibit methane formation and facilitate the C-C chain propagation, lead to the production of C2+ hydrocarbon on Ni surface.
Ultrahigh-temperature melt printing of multi-principal element alloys
Authors: Wang Xizheng , Zhao Yunhao , Chen Gang , Zhao Xinpeng , Liu Chuan , Sridar Soumya , Pizano Luis Fernando Ladinos , Li Shuke , Brozena Alexandra H. , Guo Miao , Zhang Hanlei , Wang Yuankang , Xiong Wei , Hu Liangbing 
Published: November 2022

AbstractMulti-principal element alloys (MPEA) demonstrate superior synergetic properties compared to single-element predominated traditional alloys. However, the rapid melting and uniform mixing of multi-elements for the fabrication of MPEA structural materials by metallic 3D printing is challenging as it is difficult to achieve both a high temperature and uniform temperature distribution in a sufficient heating source simultaneously. Herein, we report an ultrahigh-temperature melt printing method that can achieve rapid multi-elemental melting and uniform mixing for MPEA fabrication. In a typical fabrication process, multi-elemental metal powders are loaded into a high-temperature column zone that can be heated up to 3000 K via Joule heating, followed by melting on the order of milliseconds and mixing into homogenous alloys, which we attribute to the sufficiently uniform high-temperature heating zone. As proof-of-concept, we successfully fabricated single-phase bulk NiFeCrCo MPEA with uniform grain size. This ultrahigh-temperature rapid melt printing process provides excellent potential toward MPEA 3D printing.
CD1d-dependent rewiring of lipid metabolism in macrophages regulates innate immune responses
Authors: Brailey Phillip M. , Evans Lauren , López-Rodríguez Juan Carlos , Sinadinos Anthony , Tyrrel Victoria , Kelly Gavin , O’Donnell Valerie , Ghazal Peter , John Susan , Barral Patricia 
Published: November 2022

AbstractAlterations in cellular metabolism underpin macrophage activation, yet little is known regarding how key immunological molecules regulate metabolic programs in macrophages. Here we uncover a function for the antigen presenting molecule CD1d in the control of lipid metabolism. We show that CD1d-deficient macrophages exhibit a metabolic reprogramming, with a downregulation of lipid metabolic pathways and an increase in exogenous lipid import. This metabolic rewiring primes macrophages for enhanced responses to innate signals, as CD1d-KO cells show higher signalling and cytokine secretion upon Toll-like receptor stimulation. Mechanistically, CD1d modulates lipid import by controlling the internalization of the lipid transporter CD36, while blocking lipid uptake through CD36 restores metabolic and immune responses in macrophages. Thus, our data reveal CD1d as a key regulator of an inflammatory-metabolic circuit in macrophages, independent of its function in the control of T cell responses.
An active site loop toggles between conformations to control antibiotic hydrolysis and inhibition potency for CTX-M β-lactamase drug-resistance enzymes
Authors: Lu Shuo , Hu Liya , Lin Hanfeng , Judge Allison , Rivera Paola , Palaniappan Murugesan , Sankaran Banumathi , Wang Jin , Prasad B. V. Venkataram , Palzkill Timothy 
Published: November 2022

Abstractβ-lactamases inactivate β-lactam antibiotics leading to drug resistance. Consequently, inhibitors of β-lactamases can combat this resistance, and the β-lactamase inhibitory protein (BLIP) is a naturally occurring inhibitor. The widespread CTX-M-14 and CTX-M-15 β-lactamases have an 83% sequence identity. In this study, we show that BLIP weakly inhibits CTX-M-14 but potently inhibits CTX-M-15. The structure of the BLIP/CTX-M-15 complex reveals that binding is associated with a conformational change of an active site loop of β-lactamase. Surprisingly, the loop structure in the complex is similar to that in a drug-resistant variant (N106S) of CTX-M-14. We hypothesized that the pre-established favorable loop conformation of the N106S mutant would facilitate binding. The N106S substitution results in a ~100- and 10-fold increase in BLIP inhibition potency for CTX-M-14 and CTX-M-15, respectively. Thus, this indicates that an active site loop in β-lactamase toggles between conformations that control antibiotic hydrolysis and inhibitor susceptibility. These findings highlight the role of accessible active site conformations in controlling enzyme activity and inhibitor susceptibility as well as the influence of mutations in selectively stabilizing discrete conformations.
Chemically stable fluorescent proteins for advanced microscopy
Authors: Campbell Benjamin C. , Paez-Segala Maria G. , Looger Loren L. , Petsko Gregory A. , Liu Ce Feng 
Published: November 2022

AbstractWe report the rational engineering of a remarkably stable yellow fluorescent protein (YFP), ‘hyperfolder YFP’ (hfYFP), that withstands chaotropic conditions that denature most biological structures within seconds, including superfolder green fluorescent protein (GFP). hfYFP contains no cysteines, is chloride insensitive and tolerates aldehyde and osmium tetroxide fixation better than common fluorescent proteins, enabling its use in expansion and electron microscopies. We solved crystal structures of hfYFP (to 1.7-Å resolution), a monomeric variant, monomeric hyperfolder YFP (1.6 Å) and an mGreenLantern mutant (1.2 Å), and then rationally engineered highly stable 405-nm-excitable GFPs, large Stokes shift (LSS) monomeric GFP (LSSmGFP) and LSSA12 from these structures. Lastly, we directly exploited the chemical stability of hfYFP and LSSmGFP by devising a fluorescence-assisted protein purification strategy enabling all steps of denaturing affinity chromatography to be visualized using ultraviolet or blue light. hfYFP and LSSmGFP represent a new generation of robustly stable fluorescent proteins developed for advanced biotechnological applications.
Neuroprotective action of α-Klotho against LPS-activated glia conditioned medium in primary neuronal culture
Authors: Nakao Vinicius Wanatable , Mazucanti Caio Henrique Yokowama , de Sá Lima Larissa , de Mello Paloma Segura , de Souza Port’s Natacha Medeiros , Kinoshita Paula Fernanda , Leite Jacqueline Alves , Kawamoto Elisa Mitiko , Scavone Cristoforo 
Published: November 2022

AbstractThe α-Klotho is an anti-aging protein that, when overexpressed, extends the life span in humans and mice. It has an anti-inflammatory and protective action on renal cells by inhibiting NF-κB activation and production of inflammatory cytokines in response to TNF-α. Furthermore, studies have shown the neuroprotective effect of α-Klotho against neuroinflammation on different conditions, such as aging, animal models of neurodegenerative diseases, and ischemic brain injury. This work aimed to evaluate the effects of α-Klotho protein on primary glial cell culture against the proinflammatory challenge with LPS and how this could interfere with neuronal health. Cortical mixed glial cells and purified astrocytes were pretreated with α- α-Klotho and stimulated with LPS followed by TNFα, IL-1β, IL-6, IFN-γ levels, and NF-κB activity analysis. Conditioned medium from cortical mixed glia culture treated with LPS (glia conditioned medium (GCM) was used to induce neuronal death of primary cortical neuronal culture and evaluate if GCM-KL (medium from glia culture pretreated α-Klotho followed by LPS stimulation) or GCM + LPS in the presence of KL can reverse the effect. LPS treatment in glial cells induced an increase in proinflammatory mediators such as TNF-α, IL-1β, IL-6, and IFN-γ, and activation of astrocyte NF-κB. GCM treated-cortical neuronal culture induced a concentration-dependent neuronal death. Pretreatment with α-Klotho decreased TNF-α and IL-6 production, reverted NF-κB activation, and decreased neuronal death induced by GCM. In addition, KL incubation together with GCM + LPS completely reverts the neuronal toxicity induced by low concentration of GCM-LPS. These data suggest an anti-inflammatory and neuroprotective effect of α-Klotho protein in the CNS. This work demonstrated the therapeutic potential of α-Klotho in pathological processes which involves a neuroinflammatory component.