bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation Strategies for Triple‐Drug Combinations against Carbapenemase‐Producing Klebsiella Pneumoniae in an In Vitro Hollow‐Fiber Infection Model
Authors: Garcia Estefany , Diep John K. , Sharma Rajnikant , Hanafin Patrick O. , Abboud Cely S. , Kaye Keith S. , Li Jian , Velkov Tony , Rao Gauri G. 
Published: February 2021

Mounting antimicrobial resistance to carbapenemase‐producing Klebsiella pneumoniae (CPKP) highlights the need to optimize currently available treatment options. The objective of this study was to explore alternative dosing strategies that limit the emergence of resistance to preserve the utility of last‐line antibiotics by: (i) evaluating the pharmacodynamic (PD) killing activity of simulated humanized exposures to monotherapy and two‐drug and three‐drug combinations against CPKP bacterial isolates with different resistance mechanisms; and (ii) optimizing polymyxin B (PMB) exposure simulated in the three‐drug combination regimens to maximize the killing activity. Two CPKP clinical isolates (BAA2146 (NDM‐1) and BRKP76 (KPC‐2)) were evaluated over 168 hours using a hollow‐fiber infection model simulating clinically relevant PMB, fosfomycin, and meropenem dosing regimens. PMB‐based three‐drug combinations were further optimized by varying the initial exposure (0–24 hours) or maintenance dose received over the duration of treatment. The area under the bacterial load‐versus‐time curve (AUCFU) was used to determine PD activity. Overall reductions in PMB exposure ranged from 2 to 84%. BAA2146 and BRKP76 had median (range) AUCFUs of 11.0 (10.6–11.6) log10 CFU hour/mL and 7.08 (7.04–11.9) log10 CFU hour/mL, respectively. The PMB “front loaded” 2.5 mg/kg/day + 0.5 mg/kg maintenance dose in combination with meropenem and fosfomycin was a promising regimen against BRKP76, with an overall reduction in PMB exposure of 56% while still eradicating the bacteria. Tailored triple‐combination therapy allows for the optimization of dose and treatment duration of last‐line agents like PMB to achieve adequate drug exposure and appropriate PD activity while minimizing the emergence of resistance.
Photochemical Control of Drug Efficacy: A Comparison of Uncaging and Photoswitching Ifenprodil on NMDA Receptors
Authors: Thapaliya Ek Raj , Mony Laetitia , Sanchez Roberto , Serraz Benjamin , Paoletti Pierre , Ellis‐Davies Graham C. R. 
Published: February 2021

AbstractIfenprodil is an important negative allosteric modulator of the N‐methyl‐D‐aspartate (NMDA) receptor. We have synthesized caged and photoswitchable derivatives of this small molecule drug. Caged ifenprodil was biologically inert before photolysis, and UV irradiation efficiently released the drug allowing selective inhibition of GluN2B‐containing NMDA receptors. Azobenzene‐modified ifenprodil, on the other hand, is inert in both its trans and cis configurations, although in silico modeling predicted the trans form to be able to bind to the receptor. The disparity in effectiveness between the two compounds reflects, in part, the inherent ability of each method in manipulating the binding properties of drugs. With appropriate structure‐activity relationship uncaging enables binary control of effector binding, whereas photoswitching using freely diffusible chromophores shifts the dose‐response curve of drug‐receptor interaction. Our data suggest that the efficacy of pharmacophores having a confined binding site such as ifenprodil can be controlled more easily by uncaging in comparison to photoswitching.
Expeditious Extraction of Histones from Limited Cells or Tissue Samples and Quantitative Top‐Down Proteomic Analysis
Authors: Holt Matthew V. , Wang Tao , Young Nicolas L. 
Published: February 2021

AbstractHistones are the primary protein component of chromatin and are involved in virtually all DNA‐templated processes. Histones are abundantly post‐translationally modified by a variety of chromatin‐modifying machinery. These post‐translational modifications (PTMs) are recognized by a range of “reader” proteins, which recruit additional proteins to specific locations on chromatin and impart precise and powerful effects on gene regulation. Each PTM typically exerts a positive or negative effect on transcription, and recent studies have shown that histone PTMs function in a combinatorial histone code: that is, histone PTMs function in combination to exert precise DNA‐templated regulation. Thus, there is a need to identify and understand proteoforms, or unambiguously defined single protein molecules with all combinations of modifications. Top‐down proteomics is currently the only viable approach for identifying and quantitating histone proteoforms, and mass spectrometry instruments have become sufficiently powerful to perform these quantitative analyses in a robust and high‐throughput fashion. These recent innovations have enabled new experimental directions in chromatin research but have also introduced temporal and other constraints. This has led us to develop the protocols described here, which increase throughput, reduce sample requirements, and maintain robust quantitation. Although originally designed for high‐throughput quantitative top‐down proteomics, the protocols described here are useful for a wide range of chromatin biology applications. Starting with small amounts of cells or tissue, we describe two basic protocols for exceptionally rapid and efficient nuclei isolation, acid extraction of histones, and high‐performance liquid chromatography fractionation of histones into histone families. We additionally describe the quantitative top‐down proteomic analysis of histone H4 proteoforms. © 2021 Wiley Periodicals LLC.This article was corrected on 19 July 2022. See the end of the full text for details.Basic Protocol 1: Nuclei isolation and acid extraction of histones from mammalian cells in culture/tissuesBasic Protocol 2: HPLC fractionation of histones and histone H4 HPLC‐MS/MSSupport Protocol: Preparation of intact H3 histone tails by Glu‐C digestion
Laboratory Maintenance and Culturing of the Nematode‐Trapping Fungus Arthrobotrys oligospora
Authors: Lin Hung‐Che , Hsueh Yen‐Ping 
Published: February 2021

AbstractNematode‐trapping fungi (NTF) and nematodes are common and sympatric in nature. The molecular basis that underlies this interkingdom predator–prey interaction remains largely uncharacterized. Both NTF and nematodes can be easily isolated from soil samples. NTF do not form traps in nutrient‐rich environments, yet trap morphogenesis can be observed under nutrient‐poor conditions and upon simultaneous sensing of the nematode cues. Here, we present protocols for laboratory maintenance and culturing of the model NTF Arthrobotrys oligospora. © 2021 Wiley Periodicals LLC.This article was corrected on 19 July 2022. See the end of the full text for details.Basic Protocol 1: Growth of nematode‐trapping fungi on solid mediumBasic Protocol 2: Growth of nematode‐trapping fungi in liquid mediumBasic Protocol 3: Collection of conidia from solid mediumSupport Protocol 1: Preparation of Miracloth filter funnelBasic Protocol 4: Induction of trap morphogenesisAlternate Protocol: Quantitative measurement of trap inductionSupport Protocol 2: Preparation of synchronized C. elegans L4Basic Protocol 5: Establishing C. elegans survival rate upon exposure to A. oligosporaBasic Protocol 6: Storage of nematode‐trapping fungi strains
Identification of tolerance to metribuzin and imazethapyr herbicides in faba bean
Authors: Abou‐Khater Lynn , Maalouf Fouad , Patil Somanagouda B. , Balech Rind , Nacouzi Diana , Rubiales Diego , Kumar Shiv 
Published: February 2021

AbstractWeeds cause serious constraint to faba bean (Vicia fabaL.) productivity. Broad weed control is hampered by the availability of postemergence herbicides to control them, as the current faba bean cultivars are highly susceptible to them. Therefore, the deployment of postemergence herbicide tolerance is desirable in faba bean. To address this, 130 accessions were screened for their response in mature plants under field conditions to the recommended dosage of two herbicides, metribuzin at 250 g a.i. ha−1and imazethapyr at 75 g a.i. ha−1at Marchouch and Terbol stations. The recorded herbicide damage score (HDS) varied from 1 (no visual damage) to 5 (full damage with death of more than 50% of plants) at both locations. Low but highly significant (p< .01) and positive correlation (+0.26) was obtained between the recorded HDS at both locations. Both herbicides significantly delayed flowering and maturity time occurrence, reduced plant height and grain yield, and increased number of branches. Reduction index (RI) correlated positively with HDS score at Terbol station in different seasons and at Marchouch in 2016–2017 seasons. Eleven tolerant accessions were identified and further evaluated to 1×, 1.5×, and 2× of recommended dose of both herbicides. The results indicated that the harmful effect of herbicides on grain yield reduction intensified from 13.4 to 27.2% and from −7.6 to 1.8% as the dose of metribuzin and imazethapyr increased respectively from 250 to 500 g a.i. ha−1and from 75 to 150 g a.i. ha−1. Tolerance to metribuzin and imazethapyr in eight faba bean accessions was confirmed with no significant reduction in grain yield.
Bottom‐up Approach for Designing Cobalt Tungstate Nanospheres through Sulfur Amendment for High‐Performance Hybrid Supercapacitors
Authors: Patil Swati J. , Chodankar Nilesh R. , Huh Yun Suk , Han Young‐Kyu , Lee Dong Weon 
Published: February 2021

AbstractNanofabrication of heteroatom‐doped metal oxides into a well‐defined architecture via a “bottom‐up” approach is crucial to overcome the boundaries of the metal oxides for energy storage systems. In the present work, this issue was addressed by developing sulfur‐doped bimetallic cobalt tungstate (CoWO4) porous nanospheres for efficient hybrid supercapacitors via a single‐step, ascendable bottom‐up approach. The combined experimental and kinetics studies revealed enhanced electrical conductivity, porosity, and openness for ion migration after amendments of the CoWO4 via sulfur doping. As a result, the sulfur‐doped CoWO4 nanospheres exhibited a specific capacity of 248.5 mA h g−1 with outstanding rate capability and cycling stability. The assembled hybrid supercapacitor cell with sulfur‐doped CoWO4 nanospheres and activated carbon electrodes could be driven reversibly in a voltage of 1.6 V and exhibited a specific capacitance of 177.25 F g−1 calculated at 1.33 A g−1 with a specific energy of 63.41 Wh kg−1 at 1000 W kg−1 specific power. In addition, the hybrid supercapacitor delivered 94.85 % initial capacitance over 10000 charge‐discharge cycles. The excellent supercapacitive performance of sulfur‐doped CoWO4 nanospheres may be credited to the sulfur doping and bottom‐up fabrication of the electrode materials.
A data‐independent 9T SRAM cell with enhanced ION/IOFF ratio and RBL voltage swing in near threshold and sub‐threshold region
Authors: Gupta Monica , Gupta Kirti , Pandey Neeta 
Published: February 2021

SummaryThe conventional 8T SRAM cell with isolated read port is suggested as an alternative to overcome the read‐write conflicts associated with 6T SRAM cell. However, in near threshold and sub‐threshold regions, 8T cell performance is limited by reduced ION/IOFF ratio, deteriorated RBL voltage swing, data dependency, and higher read failures, although the existing SRAM cells address some of these issues but still suffer from degraded performance due to the trade‐off between leakage and read currents. In this paper, a 9T SRAM cell with novel read port is proposed that aims for low and data‐independent leakages, high ION/IOFF ratio, and large RBL voltage swing in near threshold and sub‐threshold regions. The performance of the proposed cell is compared with 7T, 8T, 9T, and 10T cells at 32 nm technology node by simulating a column of 128 cells to demonstrate its versatility over others. The proposed cell shows enhanced ION/IOFF ratio (71.2X), large RBL voltage swing and data‐independent leakages at VDD = 0.3 V in comparison to the conventional 8T SRAM cell. The results at different PVT corners are also captured to validate the impeccable performance of the proposed cell irrespective of operating conditions.
Preclinical evaluation of cancer immune therapy using patient‐derived tumor antigen‐specific T cells in a novel xenograft platform
Authors: Shenoy Gautam N , Greene Christopher J , Bhatta Maulasri , Baroja Miren L , Loyall Jenni L , Balu‐Iyer Sathy V , Kelleher Raymond J , Carreno Beatriz M , Linette Gerald P , Shultz Leonard D , Bankert Richard B 
Published: February 2021

AbstractObjectivesWith a rapidly growing list of candidate immune‐based cancer therapeutics, there is a critical need to generate highly reliable animal models to preclinically evaluate the efficacy of emerging immune‐based therapies, facilitating successful clinical translation. Our aim was to design and validate a novel in vivo model (called Xenomimetic or ‘X’ mouse) that allows monitoring of the ability of human tumor‐specific T cells to suppress tumor growth following their entry into the tumor.MethodsTumor xenografts are established rapidly in the greater omentum of globally immunodeficient NOD‐scid IL2Rγnull (NSG) mice following an intraperitoneal injection of melanoma target cells expressing tumor neoantigen peptides, as well as green fluorescent protein and/or luciferase. Changes in tumor burden, as well as in the number and phenotype of adoptively transferred patient‐derived tumor neoantigen‐specific T cells in response to immunotherapy, are measured by imaging to detect fluorescence/luminescence and flow cytometry, respectively.ResultsThe tumors progress rapidly and disseminate in the mice unless patient‐derived tumor‐specific T cells are introduced. An initial T cell‐mediated tumor arrest is later followed by a tumor escape, which correlates with the upregulation of the checkpoint molecules programmed cell death‐1 (PD‐1) and lymphocyte‐activation gene 3 (LAG3) on T cells. Treatment with immune‐based therapies that target these checkpoints, such as anti‐PD‐1 antibody (nivolumab) or interleukin‐12 (IL‐12), prevented or delayed the tumor escape. Furthermore, IL‐12 treatment suppressed PD‐1 and LAG3 upregulation on T cells.ConclusionTogether, these results validate the X‐mouse model and establish its potential to preclinically evaluate the therapeutic efficacy of immune‐based therapies.
2.5‐MeV neutron source controlled by high‐intensity pulsed laser generating plasma
Authors: Torrisi L. , Torrisi A. 
Published: February 2021

AbstractA laptop neutron source suited for the most demanding field or laboratory applications is presented. It is based on laser ablation of CD2 primary targets, plasma acceleration of the D+ ions, and their irradiation of secondary CD2 targets. The deuterium–deuterium (D‐D) fusion reaction is induced in the secondary target, according to the values of fusion cross‐section versus deuteron energy, which show a significant probability also at relatively low ion energies. The experiments were completed in the PALS laboratory, Prague, detecting monoenergetic neutrons at 2.45 MeV with an emission flux of about 109 neutrons per laser shot. Other experiments demonstrating the possibility to induce D‐D events were performed at IPPLM, Warsaw, and at INFN‐LNS, Catania, where the deuterons were accelerated at about 4 MeV and 50 keV, respectively. In the last case, a low laser intensity and a post‐ion acceleration system were employed. A special interaction chamber, under vacuum, is proposed to develop a new source of monochromatic neutrons or thermalized distribution of neutrons
Using priority queuing for congestion control in IoT‐based technologies for IoT applications
Authors: Oyewobi Stephen S. , Djouani Karim , Kurien Anish Matthew 
Published: February 2021

SummaryThe Internet of Things (IoT) connect millions of devices in diverse areas such as smart cities, e‐health, transportation and defense to meet a wide range of human needs. To provide these services, a large amount of data needs to be transmitted to the IoT network servers. However, the IoT networks suffer from limited resources such as buffer size, node processing capabilities, and server capacities adversely affecting throughputs, latency, and energy consumption. Additionally, the ensuing heavy network traffic due to large amount of data transmitted results in congestion which degrades IoT network performance. Therefore, innovative congestion control techniques, e.g., queue management approach needs to be developed to overcome congestion problems in IoT networks. In this paper, a novel priority queuing technique (Npqt++) is developed to control congestion in IoT networks. The Npqt++ implements a preemptive/nonpreemptive discipline with a discretion rule to classify network traffic based on their real‐time requirement into priority groups. If the discretion rule for low priority packets is satisfied, high priority packets are pushed to the front of the queue; otherwise, they wait in the queue. Our approach significantly outperforms existing techniques in terms of throughput, delay, and energy consumption.
Spectrum sensing challenges & their solutions in cognitive radio based vehicular networks
Authors: Hossain Mohammad Asif , Md Noor Rafidah , Azzuhri Saaidal Razalli , Z'aba Muhammad Reza , Ahmedy Ismail , Yau Kok‐Lim Alvin , Chembe Christopher 
Published: February 2021

SummaryVehicular ad hoc network (VANET) has been established to mitigate road collisions and traffic congestion and provide infotainment facilities to users. Allocated channels to VANET, which is the DSRC (Dedicated Short‐Range Communication), are not adequate for the full implementation of VANET. Cognitive radio (CR) can be used to alleviate this issue. CR is a programmable and intelligent radio system capable of reaching various frequency ranges. CR needs to conduct spectrum sensing to get these bands. A vehicle fitted with a CR can sense the licensed spectrum to locate the vacant spectrum (which is not used by any licensed user) when the DSRC is wholly occupied. Compared to other CR networks, VANET faces specific additional difficulties related to spectrum sensing, such as periodic topological shifts due to high‐speed mobility, multipath fading and shadowing issues, and heterogeneous quality of service (QoS) specifications. This paper explains these problems in depth. All the problems and issues were explored from the perspective of the CR focused on VANET. Probable ideas and directions to overcome these problems have also been presented. We have provided a conceptual framework for spectrum sensing. The framework resolves a variety of issues and concerns that are discussed in the paper. It gives much better results than conventional sensing techniques.
Naringin treatment improved main clozapine‐induced adverse effects in rats; emphasis on weight gain, metabolic abnormalities, and agranulocytosis
Authors: George Mina Y. , Menze Esther T. , Esmat Ahmed , Tadros Mariane G. , El‐Demerdash Ebtehal 
Published: February 2021

AbstractSchizophrenia is one of the major neuropsychiatric disorders affecting people worldwide. Unfortunately, currently available antipsychotic medications possess several side effects. Among them, clozapine is one of the atypical antipsychotics prescribed in schizophrenia wing to its blocking effect on dopamine (D2) and serotonin (5‐HT1c) receptors. However, it has been recently reserved for resistant schizophrenia due to its several side effects. The current research aimed at investigating potential naringin add‐on benefit to cease the main side effects of clozapine in ketamine‐induced psychosis in rats. In this study, schizophrenia was induced in rats via ketamine administration that could promote neuropathological patterns of schizophrenia. Afterwards, clozapine and naringin were administered to rats in order to improve such effects induced by ketamine. Clozapine administration promoted weight gain, hyperglycemia, dyslipidemia, and agranulocytosis. However, naringin was able to reduce such adverse effects when added to clozapine treatment. Naringin increased total leukocyte count preventing agranulocytosis either when administered alone or in combination with clozapine. In addition, via its metabolic activities, naringin treatment lowered serum total cholesterol and triglycerides levels. Moreover, naringin prevented weight gain when administered. Finally, naringin reduced serum glucose level preventing hyperglycemia associated with clozapine treatment. Collectively, these findings may suggest that naringin possesses a potential add‐on benefit to clozapine in treatment of schizophrenia.
Complications seen with the use of intense pulsed light sources
Authors: Agaronov Anna E. , Gold Michael 
Published: February 2021

AbstractBackgroundThe use of intense pulsed light sources has been booming in the world of cosmetic dermatology. Despite advances in technology and benefits for a wide range of skin conditions, complications do occur.ObjectiveTo assess complications associated with intense pulsed light sources in cosmetic dermatology to provide clinicians with reference to achieve better patient outcomes.MethodsA literature review of complications associated with intense pulsed light sources.ResultsNotable complications include pigmentary changes, crusting, burns, zebra appearance, folliculitis, acne, leukotrichia, paradoxical hypertrichosis, scarring, infection, and ophthalmic injury.ConclusionClinicians using intense pulsed light sources should be aware of complications associated with their use to take precautions and implement preventative strategies to avoid adverse effects and long‐term consequences.
Do dried blood spots have the potential to support result management processes in routine sports drug testing?—Part 2: Proactive sampling for follow‐up investigations concerning atypical or adverse analytical findings
Authors: Thevis Mario , Kuuranne Tiia , Thomas Andreas , Geyer Hans 
Published: February 2021

AbstractCapillary blood sampled as dried blood spot (DBS) has shown substantial potential as test matrix in sports drug testing in various different settings, enabling the analysis of numerous different drugs and/or their respective metabolites. In addition to established beneficial aspects of DBS specimens in general (such as the minimally invasive and non‐intrusive nature, and simplified sample transport), a yet unexplored advantage of DBS in the anti‐doping context could be the opportunity of preserving a source of information complementary to routine doping controls performed in urine or venous blood. Whenever follow‐up investigations are warranted or required, frequently collected and stored (but yet not analyzed) DBS samples could be target‐tested for the compound(s) in question, in order to contribute to results management and decision‐making processes.
Taking practical learning in STEM education home: Examples from do‐it‐yourself experiments in plant biology
Authors: Gya Ragnhild , Bjune Anne Elisabeth 
Published: February 2021

AbstractPractical teaching can give authentic learning experiences and teach valuable skills for undergraduate students in the STEM disciplines. One of the main ways of giving students such experiences, laboratory teaching, is met with many challenges such as budget cuts, increased use of virtual learning, and currently the university lockdowns due to the COVID‐19 pandemic. We highlight how at‐home do‐it‐yourself (DIY) experiments can be a good way to include physical interaction with your study organism, system, or technique to give the students a practical, authentic learning experience. We hope that by outlining the benefits of a practical, at‐home, DIY experiment we can inspire more people to design these teaching activities in the current remote teaching situation and beyond. By contributing two examples in the field of plant biology we enrich the database on experiments to draw inspiration from for these teaching methods.