bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overexpression of BAPT and DBTNBT genes in Taxus baccata in vitro cultures to enhance the biotechnological production of paclitaxel
Authors: Perez‐Matas Edgar , Hidalgo‐Martinez Diego , Moyano Elisabeth , Palazon Javier , Bonfill Mercedes 
Published: September 2023

SummaryPaclitaxel is one of the most effective anticancer drugs ever developed. Although the most sustainable approach to its production is provided by plant cell cultures, the yield is limited by bottleneck enzymes in the taxane biosynthetic pathway: baccatin‐aminophenylpropanoyl‐13‐O‐transferase (BAPT) and 3′‐N‐debenzoyltaxol N‐benzoyltransferase (DBTNBT). With the aim of enhancing paclitaxel production by overcoming this bottleneck, we obtained distinct lines of Taxus baccata in vitro roots, each independently overexpressing either of the two flux‐limiting genes, BAPT or DBTNBT, through a Rhizobium rhizogenes A4‐mediated transformation. Due to the slow growth rate of the transgenic Taxus roots, they were dedifferentiated to obtain callus lines and establish cell suspensions. The transgenic cells were cultured in a two‐stage system and stimulated for taxane production by a dual elicitation treatment with 1 μm coronatine plus 50 mm of randomly methylated‐β‐cyclodextrins. A high overexpression of BAPT (59.72‐fold higher at 48 h) and DBTNBT (61.93‐fold higher at 72 h) genes was observed in the transgenic cell cultures, as well as an improved taxane production. Compared to the wild type line (71.01 mg/L), the DBTNBT line produced more than four times higher amounts of paclitaxel (310 mg/L), while the content of this taxane was almost doubled in the BAPT line (135 mg/L). A transcriptional profiling of taxane biosynthetic genes revealed that GGPPS, TXS and DBAT genes were the most reactive to DBTNBT overexpression and the dual elicitation, their expression increasing gradually and constantly. The same genes exhibited a pattern of isolated peaks of expression in the elicited BAPT‐overexpressing line.
A twenty year perspective on melanoma therapy
Authors: Flaherty Keith T. 
Published: September 2023

AbstractMelanoma had long been considered to be particularly addressable with immunotherapy, but that reputation was built on modestly effective cytokine‐based immunotherapy. CTLA‐4 antibody therapy reinforced this legacy, but PD‐1 antibodies transformed the melanoma treatment landscape and lead the way for immunotherapy to become standard treatment for more than half of the advanced cancer population. BRAF mutations were discovered in 8% of all cancer and nearly 50% of melanomas. Successful development of BRAF inhibitors and BRAF/MEK combination therapy in melanoma preceded regulatory approval across all cancer types. No cancer type saw outcomes improved by the same margin as melanoma in the decade of the 2010s.
Dyschromatosis symmetrica hereditaria: A clue to early diagnosis of Aicardi–Goutières syndrome
Authors: Ahmed Fahad , Do Ngan , Vanderver Adeline L. , Treat James R. 
Published: September 2023

AbstractA 6‐year‐old female with a history of Aicardi–Goutières syndrome (AGS) presented to dermatology clinic with hypopigmented and hyperpigmented macules and patches consistent with dyschromatosis symmetrica hereditaria (DSH). Previous genetic workup demonstrated a de novo, heterozygous mutation in the adenosine deaminase acting on RNA 1 (ADAR) gene. While the co‐occurrence of AGS and DSH has previously been described in mutations of the ADAR gene, our case highlights the potential association between these disorders that may aid in earlier future diagnosis of AGS.
Information use in public administration and policy decision‐making: A research synthesis
Authors: Cantarelli Paola , Belle Nicola , Hall Jeremy L. 
Published: September 2023

AbstractThis article presents a research synthesis of 162 studies focusing on information use for decision‐making in public administration, management, and policy. The findings reveal that a significant proportion of work is centered around performance management and policy implementation. Notably, around one third of the reviewed studies adopt a behavioral science perspective. The analysis predominantly includes civil servants and citizens as the subjects, with quantitative studies outnumbering qualitative investigations by more than twofold. We identify three distinct components in understanding information use: the objective features of information architecture; the subjective mechanisms involving cognitive biases (i.e., over‐/under‐reaction to irrelevant information features) and decision noise (i.e., heterogeneity); and the moderating role of information user typology. Context should also be taken into account. The article explores how these findings relate to current societal challenges and emphasizes the potential of mixed‐methods, multisample, and/or multisite research in advancing knowledge in this area.
Slit2 suppresses endotoxin‐induced uveitis by inhibiting the PI3K/Akt/IKK/NF‐κB pathway
Authors: Du Yong , Zhou Linbin , Wen Zijun , Feng Lujia , Zhang Shaochong , Zhang Ting 
Published: September 2023

AbstractUveitis is a devastating intraocular inflammatory disease. The secreted leucine‐rich repeat protein slit homologue 2 (Slit2) has been found to be an essential regulator of inflammation. This study aimed to analyse the anti‐inflammatory effects and the underlying mechanisms of Slit2 in an endotoxin‐induced uveitis (EIU) rat model. In this study, rats with EIU pretreated recombinant human Slit2 (rhSlit2) or a control vehicle by intravitreal injection. The clinical scores were graded under a slit lamp. The protein concentrations and total number of cells in the aqueous humour (AqH) were examined, and the retinal expression of various inflammatory mediators was detected. The levels of nuclear factor‐kappa B (NF‐κB), phosphorylated NF‐κB, IkappaB‐a (IκB‐a), phosphorylated IκB‐a, IKK, phosphorylated IKK, PI3Kp85, phosphorylated PI3Kp85, Akt and phosphorylated Akt were evaluated by western blotting. Treatment with rhSlit2 dramatically diminished the clinical scores of EIU, with significant decreases in inflammatory cell infiltration, protein concentrations, cellulose‐like exudates, the production of ICAM‐1, MCP‐1, TNF‐α and IL‐6 in the AqH; and adhesion of leucocytes. The PI3K/Akt/IKK/NF‐κB pathway was found to be activated in EIU. However, the pre‐treatment of rhSlit2 significantly inhibited the production of ICAM‐1, MCP‐1, TNF‐α, and IL‐6, and inhibited leucocyte adhesion by modulating the PI3K/Akt/IKK/NF‐κB pathway. In conclusion, the intravitreal injection of rhSlit2 alleviated EIU‐related inflammation in Sprague–Dawley rats by reducing the proinflammatory cytokines and leucocyte adhesion; in particular, rhSlit2 may inhibit LPS‐induced inflammation by inhibiting the activation of PI3K/Akt/IKK/NF‐κB signalling pathway. Therefore, rhSlit2 shows significant potential for effectively alleviating immune inflammatory responses in vivo.
Low‐skilled jobs, language proficiency, and job opportunities for refugees: an experimental study
Authors: Ek Simon , Hammarstedt Mats , Skedinger Per 
Published: September 2023

AbstractIn a field experiment, we study the causal effects of previous experience and language skills when newly arrived Syrian refugees in Sweden apply for low‐skilled jobs. We find no evidence of sizable effects from previous experience or completed language classes on the probability of receiving a callback from employers. However, female applicants were more likely than males to receive a positive response. As a complement to the experiment, we interview a select number of employers, which provides additional insights into how they judge candidates for low‐skilled jobs.
Deletions within intronic T‐DNA lead to reversion of T‐DNA mutant phenotypes
Authors: Thulasi Devendrakumar Karen , Goldstein Madeleine , Kronstad James , Li Xin 
Published: September 2023

SUMMARYAgrobacterium‐mediated transformation enables random transfer‐DNA (T‐DNA) insertion into plant genomes. T‐DNA insertion into a gene's exons, introns or untranscribed regions close to the start or stop codon can disrupt gene function. Such T‐DNA mutants have been useful for reverse genetics analysis, especially in Arabidopsis thaliana. As T‐DNAs are inserted into genomic DNA, they are generally believed to be stably inherited. Here, we report a phenomenon of reversion of intronic T‐DNA mutant phenotypes. From a suppressor screen using intronic T‐DNA pi4kβ1,2 double mutant, we recovered intragenic mutants of pi4kβ1, which suppressed the autoimmunity of the double mutant. These mutants carried deletions in the intronic T‐DNAs, resulting in elevated transcription of normal PI4Kβ1. Such reversion of T‐DNA insertional mutant phenotype stresses the need for caution when using intronic T‐DNA mutants and reiterates the importance of using irreversible null mutant alleles in genetic analyses.
‘Ironing out the risk’: Assessing the effect of plateletpheresis donation frequency on iron stores in South‐Asian male donors
Authors: Madkaiker Deep , Hiregoudar Sumathi S. , Chavan Preeti , Ojha Shashank , Mendes Jennifer , Shastry Shamee 
Published: September 2023

AbstractBackground and ObjectivesRepeated blood donation is a well‐known cause of iron deficiency among donors. However, present scientific literature lacks comprehensive evidence regarding the impact of regular plateletpheresis procedures on body iron reserves. In this study, we aimed to detect and correlate iron deficiency (using iron indices) with the frequency of platelet donations. Additionally, we also analysed the correlation between other iron and haematological indices with serum ferritin to determine cost‐effective parameters that may serve as an initial screening approach to determine which donors should be subjected to serum ferritin testing.Materials and MethodsA total of 180 male participants from our platelet donor registry were enrolled in this observational cross‐sectional study. Enrolment questionnaires were administered to eligible donors, and biological samples were collected during plateletpheresis donation. Biological tests such as complete blood count, reticulocyte indices, iron indices, vitamin B12 and folate were performed.ResultsDonors with ≥12 donations per year showed the highest prevalence of low ferritin (serum ferritin: 15–30 ng/mL) and absent iron stores (serum ferritin <15 ng/mL) (41.3% and 26.7%, respectively). Ferritin showed a significant negative correlation with recent (r = −0.346) and lifetime donations (r = −0.196). The efficacy of other indices for identifying iron depletion was much better using a serum ferritin value <15 ng/mL.ConclusionRegular plateletpheresis donations can lead to varying severities of non‐anaemic iron deficiency. Blood centres must regularly monitor frequent plateletpheresis donors (especially donors with more than 11 donations in a calendar year) and ideally maintain their serum ferritin above 30 ng/mL.
Multistate outbreak of turtle‐associated salmonellosis highlights ongoing challenges with the illegal sale and distribution of small turtles
Authors: Nemechek Kaylea , Stapleton G. Sean , Waltenburg Michelle A. , Low Mabel S. F. , Gollarza Lauren , Adams Jennifer , Peralta Vi , Lopez Karen , Morrison Atisha , Schnitzler Hannah , Kline Kelly E. , McGinnis Shannon , Nichols Megin 
Published: September 2023

AbstractThe sale and distribution of small turtles (shell length <4 inches) as pets has been banned in the United States since 1975 because of the risk of Salmonella transmission, especially to children. Despite this 48‐year‐old ban, salmonellosis outbreaks continue to be linked to contact with small turtles. During investigations of turtle‐associated outbreaks, information regarding the turtle farm of origin is difficult to obtain because turtles are commonly sold by transient vendors. During 2020–2021, public health officials investigated a multistate illness outbreak caused by Salmonella enterica serotype Typhimurium linked to pet small turtles. Cases were defined as a laboratory‐confirmed Salmonella Typhimurium infection highly related (within 0–6 allele differences) to the outbreak strain based on whole‐genome sequencing analysis by core‐genome multilocus sequence typing with illness onset occurring during 27 August 2020–14 May 2021. Forty‐three patients were identified from 12 states; of these, 35% (15/43) were children <5 years old. Among patients with available information, 37% (14/38) were hospitalized, and one death was reported. Seventy‐four percent (25/34) of patients reported turtle exposure in the week before illness onset, and 84% (16/19) specified exposure to small turtles. The outbreak strain was isolated from samples collected from a Pennsylvania patient's small turtle tank. Two patients reported purchasing their small turtles from pet stores. Salmonella Braenderup was isolated from samples collected from small turtles and their habitat at one of these stores; however, at that time, this strain was not associated with any human illnesses. This investigation was notable because of the documented sale of small turtles from several pet stores combined with the identification of a single small turtle supplier to these pet stores. The high proportion of children involved in this outbreak highlights the continued need to educate the pet industry as well as parents and caregivers about the risk of turtle‐associated salmonellosis especially in children. Understanding and addressing the persisting challenges related to the illegal sale and distribution of small turtles could reduce the burden of turtle‐associated salmonellosis.
The substantia nigra modulates proximal colon tone and motility in a vagally‐dependent manner in the rat
Authors: Xing Tiaosi , Nanni Giorgia , Burkholder Cameron R. , Browning Kirsteen N. , Travagli R. Alberto 
Published: September 2023

AbstractA monosynaptic pathway connects the substantia nigra pars compacta (SNpc) to neurons of the dorsal motor nucleus of the vagus (DMV). This monosynaptic pathway modulates the vagal control of gastric motility. It is not known, however, whether this nigro‐vagal pathway also modulates the tone and motility of the proximal colon. In rats, microinjection of retrograde tracers in the proximal colon and of anterograde tracers in SNpc showed that bilaterally labelled colonic‐projecting neurons in the DMV received inputs from SNpc neurons. Microinjections of the ionotropic glutamate receptor agonist, NMDA, in the SNpc increased proximal colonic motility and tone, as measured via a strain gauge aligned with the colonic circular smooth muscle; the motility increase was inhibited by acute subdiaphragmatic vagotomy. Upon transfection of SNpc with pAAV‐hSyn‐hM3D(Gq)‐mCherry, chemogenetic activation of nigro‐vagal nerve terminals by brainstem application of clozapine‐N‐oxide increased the firing rate of DMV neurons and proximal colon motility; both responses were abolished by brainstem pretreatment with the dopaminergic D1‐like antagonist SCH23390. Chemogenetic inhibition of nigro‐vagal nerve terminals following SNpc transfection with pAAV‐hSyn‐hM4D(Gi)‐mCherry decreased the firing rate of DMV neurons and inhibited proximal colon motility. These data suggest that a nigro‐vagal pathway modulates activity of the proximal colon motility tonically via a discrete dopaminergic synapse in a manner dependent on vagal efferent nerve activity. Impairment of this nigro‐vagal pathway may contribute to the severely reduced colonic transit and prominent constipation observed in both patients and animal models of parkinsonism.
imageKey points
Substantia nigra pars compacta (SNpc) neurons are connected to the dorsal motor nucleus of the vagus (DMV) neurons via a presumed direct pathway.
Brainstem neurons in the lateral DMV innervate the proximal colon. Colonic‐projecting DMV neurons receive inputs from neurons of the SNpc.
The nigro‐vagal pathway modulates tone and motility of the proximal colon via D1‐like receptors in the DMV.
The present study provides the mechanistic basis for explaining how SNpc alterations may lead to a high rate of constipation in patients with Parkinson's Disease.
Windage Loss Models for Enclosed Cylindrical Flows Under S-CO2 Condition
Authors: Kim Dokyu , Jeong Yongju , Son In Woo , Lee Jeong Ik 
Published: September 2023

Abstract
A supercritical CO2 (S-CO2) Brayton cycle is expected to have high compactness, simple configuration, and competitive efficiency. These advantages originated from CO2 nonideal gas properties near the critical point. However, the strong real gas effect makes the design challenging. Among components, turbomachinery is most affected by the real gas effects of S-CO2. In order to obtain accurate design of the turbomachinery, accurate loss models are needed. Windage loss is one of the external losses that determines the motor load and is responsible for heat generation due to friction. The overall turbomachinery efficiency is greatly affected by the windage loss especially in an S-CO2 power cycle due to high fluid density and high rotational speed. Therefore, an accurate windage loss model that can reflect the real gas effect of CO2 near the critical point is essential to obtain accurate design of the turbomachinery as well as the power cycle. In this paper, existing windage loss models are compared under S-CO2 conditions first, and the applicability of each model is evaluated. The comparison is to understand how much turbomachinery performance uncertainty can be expected due to the windage loss models and to suggest the way to improve the models.
Turbulent Flame Speed and Flame Characteristics of Lean Premixed H2-CH4 Flames at Moderate Pressure Levels
Authors: Faldella Filippo , Eisenring Sebastian , Kim Taesung , Doll Ulrich , Jansohn Peter 
Published: September 2023

Abstract
Carbon dioxide emissions in gas turbine power generation can be reduced by adding an increasing amount of hydrogen to the existing natural gas-fueled combustion systems. To enable safe operation, more insight on how H2 addition affects turbulent flame speed and other important flame characteristics is needed. In this work, the investigation of hydrogen addition effects on certain flame properties has been carried out in a high-pressure axial-dump combustor at gas turbine relevant conditions. OH planar laser induced fluorescence (PLIF) was applied to retrieve flame front contours and turbulent flame speed. The results show that as the concentration of hydrogen in the fuel mixture increases, turbulent flame speed and flame characteristics change drastically. Two main regimes can be identified: From 0 to 50% vol. Hydrogen, the turbulent flame speed increases weakly in an almost linear fashion, while from 50% vol. to 100% vol. the trend sharply changes and the higher reactivity of hydrogen, combined with a lower Lewis number, cause thermal-diffusive instability and preferential diffusion effects to become increasingly strong, leading to very high burning rates. The presented results help to understand and to define the relevant modifications that are necessary to successfully operate gas turbine combustor systems with high H2 content fuels.
Integrated Aerodynamic and Mechanical Design of a Large-Scale Axial Turbine Operating With A Supercritical Carbon Dioxide Mixture
Authors: Abdeldayem Abdelrahman , Paggini Andrea , Diurno Tommaso , Orazi Claudio , White Martin , Ruggiero Marco , Sayma Abdulnaser 
Published: September 2023

Abstract
In this paper, the design of a large-scale axial turbine operating with supercritical carbon dioxide (sCO2) blended with sulfur dioxide (SO2) is presented considering aerodynamic and mechanical design aspects as well as the integration of the whole turbine assembly. The turbine shaft power is 130 MW, designed for a 100 MWe concentrated-solar power plant with turbine inlet conditions of 239.1 bar and 700 °C, total-to-static pressure ratio of 2.94, and mass-flow rate of 822 kg/s. The aerodynamic flow path, obtained in a previous study, is first summarized before the aerodynamic performance of the turbine is evaluated using both steady-state and unsteady three-dimensional numerical models. Whole-annulus unsteady simulations are performed for the last turbine stage and the exhaust section to assess the unsteady loads on the rotor due to downstream pressure field distortion and to assess the aerodynamic losses within the diffuser and exhaust section. The potential low engine order excitation at the last rotor stage natural frequency modes due to downstream pressure distortion is assessed. The design of the turbine assembly is constrained by current manufacturing capabilities and the properties of the proposed working fluid. High-level flow-path design parameters, such as pitch diameter and number of stages, are established considering a trade-off between weight and footprint, turbine efficiency, and rotordynamics. Rotordynamic stability is assessed considering the high fluid density and related cross coupling effects. Finally, shaft end sizing, cooling system design, and the integration of dry gas seals are discussed.
Performance Investigation of Stator-Less and Blade-Less Radial Expander
Authors: Renuke Avinash , Traverso Alberto , Reggio Federico , Pascenti Matteo , Silvestri Paolo 
Published: September 2023

Abstract
Interests in small-scale turbomachinery are gaining momentum, particularly around waste heat recovery using Organic Rankine Cycle (ORC), energy harvesting, pico-hydro, refrigeration and heat pumps and small-scale power generation. These applications demand to have economical, simple construction, and reasonably efficient machines. The performance of bladed turbomachine at a small scale is poor mainly due to viscous losses and relatively large clearances. In some cases, like ORC, it requires a lubrication system, making it complex and costly. Bladeless or Tesla turbomachinery is seen as one of the solutions for these applications due to its simple construction and cost-effectiveness. However, the experimental efficiency of the bladeless turbines/compressors is found in the low region, &lt;40%. In this article, the performance of a bladeless turbine is investigated using a vaneless volute configuration, making the turbine stator-less (vaneless volute) and bladeless (vaneless rotor). This study presents numerical and experimental performance investigation with a volute as a stator of the bladeless rotor. Three-dimensional (3D) Numerical results show very promising performance of the turbine with total to static efficiencies calculated above 65%. In the second part of the article, turbine prototype components, assembly, and test setup are discussed. Experimental maximum efficiency of 41.5 ± 0.88% at 3.5 kg/s@5000 rpm and power of 915 W is obtained. This is the highest recorded efficiency for the Tesla turbine in peer-reviewed research. The overall turbine performance from 3D numerical simulation with ventilation and mechanical losses is compared with experimental results. This work demonstrates that the proposed stator-less/volute configuration provides an efficient way for bladeless or Tesla turbines, particularly for low-head applications.