bluuebunny/crossref_metadata_2025 huggingface dataset:
Aspartame effect in sickle cell anemia
Authors: Manion Carl V. , Howard Jessica , Ogle Brandi , Parkhurst Joan , Edmundson Allen
Published: July 2002

Objective

To examine the in vitro and in vivo attributes of aspartame and to determine its efficacy for treating sickle cell anemia.

Rationale

Aspartame (L‐aspartyl‐L‐phenylalanine methyl ester) binds with 2 human Bence Jones proteins. The proteins (Mcg and Sea) showed phenylalanine penetrating into hydrophobic binding sites. This aspartame property suggested a potential to interfere with sickle hemoglobin fibril formation.

Methods

For the in vitro studies, blood from 20 subjects monitored for sickle cell anemia was collected in heparinized tubes. Specimens were divided in thirds and aspartame was added to 2 tubes to yield a 1 mg/mL or 2 mg/mL concentration. Sickled cells that were present after a drop from each aliquot was added to a fresh 2% metabisulfite solution were counted 3 times. For the in vivo studies, 23 subjects from the Sickle Cell Clinic (University of Oklahoma Health Sciences Center, Oklahoma City, Okla) consented to participate in a randomized single‐dose administration of 1.5, 3.0, or 6 mg/kg aspartame. Heparinized blood was obtained at 0, 30, 60, 120, 240, 480, and 1440 minutes after aspartame administration. Specimens were counted in a blinded manner by means of the technique used for the in vitro method, but a photomicrograph of 1 field from each triplicate count was made. The pictures were marked and were computer counted.

Results

For the in vitro studies, sickled cells decreased from 28% to <14% when 1 mg/mL aspartame was added and decreased further with 2 mg/mL. For the in vivo studies, a decreased number of sickled cells in homozygous blood (HbSS) were observed after oral administration of aspartame. Sickling was inhibited by 6 mg/kg aspartame for at least 6 hours in 15 subjects with HbSS anemia.

Conclusions

Further evaluations of the efficacy of aspartame for sickle crisis and crisis prevention appears to be warranted.

Clinical Pharmacology & Therapeutics (2001) 69, 346–355; doi: 10.1067/mcp.2001.115141
Removal of digoxin by column for specific adsorption of β2‐microglobulin: A potential use for digoxin intoxication
Authors: Tsuruoka Shuichi , Osono Eiichi , Nishiki Kenta , Kawaguchi Atsuhiro , Arai Tatsuhiko , Furuyoshi Sigeo , Saito Tetsuo , Takata Satoru , Sugimoto Koichi , Kurihara Satoshi , Fujimura Akio
Published: July 2002

Background

A β2‐microglobulin adsorption column used for the treatment of dialysis‐related amyloidosis removes serum β2‐microglobulin by recognition of lipophilic residue in the protein. No data are available for the adsorption of the highly lipophilic drug digoxin.

Methods

In vivo clearance of digoxin with the β2‐microglobulin column was measured by a single use of the column in 8 patients receiving hemodialysis with a therapeutic level of digoxin. In vitro adsorption was evaluated by use of incubation with adsorbent of the column and digoxin or ranitidine, a hydrophilic drug. Clearance with the β2‐microglobulin column was further compared with that obtained by use of activated charcoal in the dogs intoxicated with digoxin.

Results

Digoxin concentration was reduced from 1.11 ± 0.25 ng/mL to 0.57 ± 0.15 ng/mL at 240 minutes after initiation of hemoperfusion with the column in the patients. Digoxin clearance with the β2‐microglobulin column was about 145 ± 20 mL/min, with a blood flow rate of 160 to 220 mL/min (80% of plasma flow rate). Eighty‐five percent of digoxin was adsorbed in vitro, and the capacity of the β2‐microglobulin column was not saturated until a toxic level was reached (50 ng/mL). This value was higher than that obtained with use of charcoal. In dogs with digoxin intoxication, digoxin clearance was 38.9 ± 1.5 mL/min, with a blood flow rate of 50 mL/min (95% of plasma flow rate), which was almost twice as that achieved with charcoal. The degree of thrombocytopenia and leukopenia was small with use of the β2‐microglobulin column.

Conclusion

These data suggested that the β2‐microglobulin column selectively adsorbs digoxin. This column is a promising tool for the treatment of digoxin intoxication, especially in patients undergoing hemodialysis.

Clinical Pharmacology & Therapeutics (2001) 69, 422–430; doi: 10.1067/mcp.2001.116061
Designing Copper‐Based Catalysts for Efficient Carbon Dioxide Electroreduction
Authors: Wang Yuhang , Liu Junlang , Zheng Gengfeng
Published: April 2021

The electroreduction of carbon dioxide (CO2) has been emerging as a high‐ potential approach for CO2 utilization using renewables. When copper (Cu) based catalysts are used, this platform can produce multi‐carbon (C2+) fuels and chemicals with almost net‐zero emission, contributing to the closure of the anthropogenic carbon cycle. Nonetheless, the rational design and development of Cu‐based catalysts are critical toward the realization of highly selective and efficient CO2 electroreduction. In this review, first the latest advances in Cu‐catalyzed CO2 electroreduction in the product selectivity and electrocatalytic activity are briefly summarized. Then, recent theoretical and mechanistic studies of CO2 electroreduction on Cu‐based catalysts are investigated, which serve as programs to design catalysts. Strategies for devising Cu catalysts that aim at promoting different key elementary steps for hydrocarbon and C2+ oxygenates production are further summarized. Moreover, challenges in understanding the mechanism, operando investigation of Cu catalysts and reactions, and systems’ influences are also presented. Finally, the future prospects of CO2 electroreduction are discussed.
Preparation and properties of styrene ethylene butylene styrene / polypropylene thermoplastic elastomer powder for selective laser sintering 3D printing
Authors: He Zuhan , Ren Chuanzheng , Zhang Aimin , Bao Jianjun
Published: April 2021

As one of the most important thermoplastic elastomer materials, the application of styrene ethylene butylene styrene (SEBS) in selective laser sintering (SLS) has not been reported. In this study, SEBS and polypropylene (PP) are blended and then pulverized at low temperatures. We find that SEBS with high molecular weight and styrene segment content is difficult to melt and flow under laser irradiation, which is not suitable for SLS 3D printing. SEBS with low molecular weight can be printed, and its tensile properties can reach 2.1Mpa and 134% elongation at break. We test the enhanced absorption effect of two different infrared absorbers and find that graphene (GE) can enhance absorption mainly rely on its special structure to increase the optical path of the laser. The absorption enhancement effect of each enhancer rises first and then decreases. 0.4‰ addition of GE can bring 22.5% enhancement. With the enhancement of GE, we get a product of 2.8 MPa tensile strength and 176% elongation at break.
An Adaptive Blended Learning Model for the Implementation of an Integrated Medical Neuroscience Course During the Covid‐19 Pandemic
Authors: Nathaniel Thomas I. , Goodwin Richard L . , Fowler Lauren , McPhail Brooks , Black Asa C.
Published: April 2021

The implementation of an integrated medical neuroscience course by technologically pivoting an in‐person neuroscience course to online using an adaptive blended method may provide a unique approach for teaching a medical neuroscience course during the Covid‐19 pandemic. An adaptive blended learning method was developed in response to the requirements necessitated by the Covid‐19 pandemic. This model combined pedagogical needs with digital technology using online learning activities to implement student learning in a medical neuroscience course for year one medical students. This approach provided medical students with an individually customized learning opportunity in medical neuroscience. The students had the complete choice to engage the learning system synchronously or asynchronously and learn neuroscience materials at different locations and times in response to the demands required to deal with the pandemic. Students' performance in summative and formative examinations of the adaptive blended learning activities were compared with the previous performance obtained the previous year when the contents of the medical neuroscience course were implemented using the conventional “face‐to‐face” learning approach. While the cohort of our students in 2019 and 2020 changed, the contents, sessions, volume of material, and assessment were constant. This enabled us to compare the results of the 2019 and 2020 classes. Overall, students' performance was not significantly different between the adaptive blended learning and the in‐person approach. More students scored between 70% and 79% during the adaptive blended learning compared with in‐class teaching, while more students scored between 80% and 89% during the in‐person learning than during the adaptive blended learning. Finally, the percentage of students that scored >90% was not significantly different for both Years 2019 and 2020. The adaptive blended learning approach was effective in enhancing academic performance for high‐performing medical students. It also permitted the early identification of underachieving students, thereby serving as an early warning sign to permit timely intervention.
Exploring the structure–function relationship in a hypothetical membrane protein from a nucleotide sequence
Authors: Osorio Manuel I. , Salinas Dino G.
Published: April 2021

An educational activity is proposed that uses software for proteomic analysis and databases available for free on the Internet to estimate the structure and function of a hypothetical protein from its coding nucleotide sequence. This bioinformatics activity is recommended for integrated introductory courses that address the structure function relationship in proteins.
Gluconeogenesis is reduced from alanine, lactate and pyruvate, but maintained from glycerol, in liver perfusion of rats with early and late sepsis
Authors: de Souza Galia Winny Beatriz , Biazi Giuliana Regina , Frasson‐Uemura Isabele Gonçalves , Miksza Daniele Romani , Zaia Cássia Thaïs Bussamra Vieira , Zaia Dimas Augusto Morozin , de Souza Helenir Medri , Bertolini Gisele Lopes
Published: April 2021

Sepsis induces several metabolic abnormalities, including hypoglycaemia in the most advanced stage of the disease, a risk factor for complications and death. Although hypoglycaemia can be caused by inhibition of hepatic gluconeogenesis, decreased and increased gluconeogenesis were reported in sepsis. Furthermore, gluconeogenesis from glycerol was not yet evaluated in this disease. The main purpose of this study was to investigate the gluconeogenesis from alanine, lactate, pyruvate and glycerol in rats with early (8 hours) and late (18 hours) sepsis. Parameters related to the characterization of sepsis were also evaluated. Sepsis was induced by cecal ligation and puncture and gluconeogenesis was assessed in liver perfusion. Rats with early and late sepsis showed increased lactataemia, depletion of liver glycogen and peripheral insulin resistance, characterizing the establishment of sepsis. Rats with early and late sepsis showed decreased gluconeogenesis from alanine, lactate and pyruvate. Interestingly, gluconeogenesis from glycerol, a precursor that enters in the pathway at a later step, subsequent to the entry of alanine, lactate and pyruvate, was maintained in rats with early and late sepsis. In conclusion, gluconeogenesis is decreased from alanine, lactate and pyruvate, but maintained from glycerol, in liver perfusion of rats with early and late sepsis.

Significance of the study

The maintenance of gluconeogenesis from glycerol, but not from alanine, lactate and pyruvate, together with the liver glycogen depletion, points the glycerol as an important precursor for the maintenance of glycaemic homeostasis in sepsis. The findings open the possibility of further investigation on the administration of glycerol in the treatment of hypoglycaemia associated with more advanced sepsis.
Localised release of matrix metallopeptidase 8 in fatal cerebral malaria
Authors: Georgiadou Athina , Naidu Praveena , Walsh Sophie , Kamiza Steve , Barrera Valentina , Harding Simon P , Moxon Christopher A , Cunnington Aubrey J
Published: April 2021

Objective

Cerebral malaria (CM) is a complication of Plasmodium falciparum malaria, in which progressive brain swelling is associated with sequestration of parasites and impaired barrier function of the cerebral microvascular endothelium. To test the hypothesis that localised release of matrix metallopeptidase 8 (MMP8) within the retina is implicated in microvascular leak in CM, we examined its expression and association with extravascular fibrinogen leak in a case–control study of post‐mortem retinal samples from 13 Malawian children who met the clinical case definition of CM during life. Cases were seven children who were found on post‐mortem examination to have ‘true‐CM’ (parasite sequestration in brain blood vessels), whilst controls were six children who had alternative causes of death (‘faux‐CM’, no parasite sequestration in blood vessels).

Methods

We used immunofluorescence microscopy and independent scoring, by two assessors blinded to the CM status, to assess MMP8 expression, extravascular fibrinogen as an indicator of vascular leak and their co‐localisation in the retinal microvasculature.

Results

In ‘true‐CM’ subjects, MMP8 staining was invariably associated with sequestered parasites and a median of 88% (IQR = 74–91%) of capillaries showed MMP8 staining, compared with 14% (IQR = 3.8–24%) in ‘faux‐CM’ (P‐value = 0.001). 41% (IQR = 28–49%) of capillaries in ‘true‐CM’ subjects showed co‐localisation of extravascular fibrinogen leak and MMP8 staining, compared with 1.8% of capillaries in ‘faux‐CM’ (IQR = 0–3.9%, P‐value = 0.01). Vascular leak was rare in the absence of MMP8 staining.

Conclusion

Matrix metallopeptidase 8 was extensively expressed in retinal capillaries of Malawian children with malarial retinopathy and strongly associated with vascular leak. Our findings implicate MMP8 as a cause of the vascular endothelial barrier disruption in CM, which may precipitate fatal brain swelling.
Optimal power allocation‐based novel control jamming scheme for nonorthogonal multiple access enabled decode‐and‐forward relay network
Authors: Narasimha Nayak V. , Gurrala Kiran Kumar
Published: April 2021

In this work, a new control jamming (CJ) scheme has been proposed for a cooperative nonorthogonal multiple access (NOMA) network with optimal power allocation factors by employing decode‐and‐forward (DF) relay. Maximization of secrecy rate at both NOMA users with the aid of CJ under total transmit power constraint is considered as an optimization problem. In this regard, invasive weed optimization (IWO) algorithm‐based approach is proposed to facilitate optimal power allocation for the considered network. In this analysis, performance metric secrecy rate is analyzed with CJ at both NOMA users by varying the location of eavesdropper with respect to the relay and jammer. In addition, the performance of fixed power allocation (FPA) and proposed power allocation (PPA) schemes is investigated with CJ and compared with jamming (J) and without jamming (WJ) conditions. Simulation result analysis specifies that secrecy performance is enhanced remarkably by CJ and PPA outperforms the FPA.
Site‐specific liquefaction fragility analysis: Cloud, stripe, and incremental approaches
Authors: Bullock Zach , Liel Abbie B. , Porter Keith A. , Dashti Shideh
Published: April 2021

This article adapts a handful of procedures from performance‐based earthquake engineering for use in estimating the probability of liquefaction triggering. The resulting approach, defined as liquefaction fragility analysis (LFA), produces site‐specific fragility functions for liquefaction. These fragility functions incorporate site‐specific, system‐level effects not captured by existing, broader methods, but require more detailed knowledge of both the subsurface conditions and the seismic hazard at the site. LFA accounts for system‐level effects such as pore pressure migration, dynamic layer‐to‐layer interaction, and partial saturation to the extent that these phenomena can be captured in the constitutive models used in nonlinear site response analyses. Multiple approaches for selecting ground motions for LFA are discussed and illustrated using a case study of a site in Los Angeles, California. The computational expense of using LFA for probabilistic estimate of future liquefaction seismic performance is also discussed.
Population Pharmacokinetic‐Pharmacodynamic Modeling and Covariate Analyses of Neutropenia and Thrombocytopenia in Patients With Solid Tumors Treated With Lurbinectedin
Authors: Fernández‐Teruel Carlos , Lubomirov Rubin , Fudio Salvador
Published: April 2021

Lurbinectedin is a selective inhibitor of oncogenic transcription. Reversible myelosuppression is its most relevant toxicity. Pharmacokinetic‐pharmacodynamic analyses were conducted to characterize the time course of absolute neutrophil count and platelet count recovery and to detect and quantify the effect of relevant covariates in patients with advanced solid tumors treated with lurbinectedin. Absolute neutrophil count, platelet count, and lurbinectedin total plasma concentration were assessed in 244 patients treated with lurbinectedin with varied dosing schedules and doses. A reference extended semimechanistic pharmacokinetic‐pharmacodynamic model of myelosuppression was used. Granulocyte colony‐stimulating factor (G‐CSF) administration was modeled as a dichotomous covariate, and platelet transfusions were included as a bolus dose into the last compartment of the model, representing the central circulation. Final models were suitable to describe the time course of absolute neutrophil count and platelet count recovery. A lurbinectedin dose of 3.2 mg/m2 every 3 weeks can be administered without primary prophylaxis with G‐CSF. G‐CSF followed by ≤2 dose reductions of 20%, if needed, gradually reduced grade 4 neutropenia from cycle 3 onward. BSA‐based dosing reduced the incidence of grade ≥ 3 thrombocytopenia. One‐week dose delays because of low absolute neutrophil count occurred in 3.5% of patients, thus supporting every‐3‐week administration. CYP3A inhibitors produced absolute 11.0% and 6.2% increases in grade ≥ 3 neutropenia and thrombocytopenia, respectively. Neutropenia and thrombocytopenia after lurbinectedin administration to cancer patients are noncumulative, reversible, short lasting, and clinically manageable with secondary prophylaxis of G‐CSF or platelet transfusion and, if needed, dose reductions.
Evaluation of the effects of two different indirect bonding methods on strength of the brackets in mandibular model of severe anterior crowding
Authors: Yuzbasioglu Ertugrul Betul , Alkan Özer
Published: April 2021

An indirect bonding method was developed to solve the problems likely to be encountered during proper positioning of the brackets. The aim of this study is to compare two different indirect bonding methods on the bond strength of the brackets. A 160 extracted human lower incisors were assigned into two groups. Transparent silicone material and bioplast material were used in transfer tray preparation in groups 1 and 2, respectively. Transbond XT adhesive system was used to bond brackets to teeth in both groups. A high intensity LED light source was used for 3 s for adhesive polymerization. Brackets were subjected to shear forces with universal test machine under 0.5 mm/min crosshead speed until failure. Adhesive Remnant Index was used to assess the amount of adhesive remnant on enamel surface after shear test under 10× magnification. Two subjects from both groups were evaluated for enamel surface characteristics with scanning electron microscope (SEM). Mean shear bond strengths were found to be 5.13 ± 1.8 MPa and 5.93 ± 2.19 MPa for silicone and bioplast groups, respectively. Bioplast group showed significantly greater shear bond strength than that of the silicone group. Maximum ARI score, assessed under ×10 magnification was 3 in both groups. A score of 3 was significantly more frequent in bioplast group. Differences were seen between the groups in terms of enamel surface characteristics under SEM evaluation. It was determined that bioplast material, which is considered to be the gold standard for the indirect bonding method, has greater shear bond strength than silicone material.
The virulence factor GroEL directs the osteogenic and adipogenic differentiation of human periodontal ligament stem cells through the involvement of JNK/MAPK and NF‐κB signaling
Authors: Zhang Li , Cheng Lei , Cui Yujia , Wu Zuping , Cai Linyi , Yang Liu , Duan Mengmeng , Zhang Demao , Zhou Chenchen , Xie Jing
Published: April 2021

Background

GroEL, a bacterial metabolite, is an important stimulator of inflammation. The aim of this study is to confirm the effect of the virulence factor GroEL on differentiation potential of periodontal ligament (PDL) stem cells (PDLSCs) and the potential mechanisms.

Methods

PDLSCs were obtained from extracted human premolars. GroEL was administered to osteogenic‐ and adipogenic‐induced hPDLSCs. Alkaline phosphatase (ALP) staining, Alizarin Red staining and Oil Red staining were performed. Gene and protein expression were separately measured by qPCR and Western blotting. The expression and localization of activated signaling factors were confirmed by immunofluorescence staining. The inhibitors of myeloid differentiation factor 88 (MyD88, an adaptor protein of TLRs), JNK/MAPK and NF‐κB signaling were used to verify their specific effects.

Results

First, we found that GroEL inhibited the osteogenic differentiation and enhanced the adipogenic differentiation of hPDLSCs. Next, we found that GroEL increased the expression of TLR2 and TLR4 and GroEL activated JNK/MAPK and NF‐κB signaling, which can be blocked by inhibition of MyD88. Finally, we found that inhibition of MyD88 restored GroEL‐induced osteogenic and adipogenic differentiation and blocking JNK/MAPK or NF‐κB signaling partly restored GroEL effects.

Conclusion

In the current study, we revealed a potential interaction between bacteria and host cells by showing that GroEL directs the osteogenic and adipogenic differentiation of hPDLSCs by the involvement of JNK/MAPK and NF‐κB signaling. This study provides evidence that bacterial products can influence the differentiation of stem cells and reveals potential effect of GroEL on the context of tissue regeneration.
UPLC‐MS/MS‐based plasma lipidomics reveal a distinctive signature in systemic lupus erythematosus patients
Authors: Chen Jiaxi , Liu Chong , Ye Shenyi , Lu Ruyue , Zhu Hongguo , Xu Jiaqin
Published: April 2021

Global lipidomics is of considerable utility for exploring altered lipid profiles and unique diagnostic biomarkers in diseases. We aim to apply ultra‐performance liquid chromatography‐tandem mass spectrometry to characterize the lipidomics profile in systemic lupus erythematosus (SLE) patients and explore the underlying pathogenic pathways using the lipidomics approach. Plasma samples from 18 SLE patients, 20 rheumatoid arthritis (RA) patients, and 20 healthy controls (HC) were collected. A total of 467 lipids molecular features were annotated from each sample. Orthogonal partial least square‐discriminant analysis, K‐mean clustering analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated disrupted lipid metabolism in SLE patients, especially in phospholipid, glycerol, and sphingolipid metabolism. The area under curve (AUC) of lipid metabolism biomarkers was better than SLE inflammation markers that ordinarily used in the clinic. Proposed model of monoglyceride (MG) (16:0), MG (18:0), phosphatidylethanolamine (PE) (18:3–16:0), PE (16:0–20:4), and phosphatidylcholine (PC) (O‐16:2–18:3) yielded AUC 1.000 (95% CI, 1.000–1.000), specificity 100% and sensitivity 100% in the diagnosis of SLE from HC. A panel of three lipids molecular PC (18:3‐18:1), PE (20:3–18:0), PE (16:0–20:4) permitted to accurately diagnosis of SLE from RA, with AUC 0.921 (95% CI, 0.828–1.000), 70% specificity, and 100% sensitivity. The plasma lipidomics signatures could serve as an efficient and accurate tool for early diagnosis and provide unprecedented insight into the pathogenesis of SLE.
Characterization of kaposiform lymphangiomatosis tissue‐derived cells
Authors: Nozawa Akifumi , Ozeki Michio , Yasue Shiho , Endo Saori , Noguchi Kei , Kanayama Tomohiro , Tomita Hiroyuki , Aoki Yoko , Ohnishi Hidenori
Published: April 2021

Background

Kaposiform lymphangiomatosis (KLA) is a recently characterized systemic lymphatic anomaly. Activation of RAS/MAPK and PI3K/AKT/mTOR pathways may affect KLA pathogenesis, but the cellular basis of KLA is unclear. Abnormal‐spindle endothelial cells that express lymphatic endothelial cell (LEC) markers are characteristic of KLA histopathology. This study evaluated patient‐derived KLA cells to establish their morphological and biological characteristics.

Procedure

We established cell lines from primary KLA tissues of two patients with KLA and examined their morphological and functional characteristics, messenger RNA and protein expression profiles, gene mutations, and responses to inhibitors of the RAS/MAPK and PI3K/AKT/mTOR pathways.

Results

Both KLA cell lines showed spindle‐shaped morphology, stained positive for podoplanin (PDPN), and exhibited impaired tube‐formation properties. They expressed LEC marker PDPN and mesenchymal stem cell markers (CD90, CD105) in the absence of endothelial cell markers (CD34, CD31, VWF), per real‐time polymerase chain reaction. Both mTOR inhibitor rapamycin and MEK inhibitor trametinib inhibited growth of the two cell lines. A NRAS p.Q61R variant was found in one of two independent KLA tissue samples, but not in the KLA cells (per targeted next‐generation sequencing); and KLA cells with this variant had elevated AKT phosphorylation levels. ERK phosphorylation levels were undetectable in both KLA cell lines.

Conclusions

Inhibition of the RAS/MAPK and PI3K/AKT/mTOR pathways may represent potential therapeutic targets in KLA. These patient‐derived KLA cell lines will be useful research tools to elucidate KLA etiology, and could pave the way for basic, translational, and preclinical studies of this disease.
Transition metal cation inhibition of Mycobacterium tuberculosis esterase RV0045C
Authors: Bowles Isobel E. , Pool Emily H. , Lancaster Benjamin S. , Lawson Emily K. , Savas Christopher P. , Kartje Zach J. , Severinac Luke , Cho David H. , Macbeth Mark R. , Johnson R. Jeremy , Hoops Geoffrey C.
Published: April 2021

Mycobacterium tuberculosis virulence is highly metal‐dependent with metal availability modulating the shift from the dormant to active states of M. tuberculosis infection. Rv0045c from M. tuberculosis is a proposed metabolic serine hydrolase whose folded stability is dependent on divalent metal concentration. Herein, we measured the divalent metal inhibition profile of the enzymatic activity of Rv0045c and found specific divalent transition metal cations (Cu2+ ≥ Zn2+ > Ni2+ > Co2+) strongly inhibited its enzymatic activity. The metal cations bind allosterically, largely affecting values for kcat rather than KM. Removal of the artificial N‐terminal 6xHis‐tag did not change the metal‐dependent inhibition, indicating that the allosteric inhibition site is native to Rv0045c. To isolate the site of this allosteric regulation in Rv0045c, the structures of Rv0045c were determined at 1.8 Å and 2.0 Å resolution in the presence and absence of Zn2+ with each structure containing a previously unresolved dynamic loop spanning the binding pocket. Through the combination of structural analysis with and without zinc and targeted mutagenesis, this metal‐dependent inhibition was traced to multiple chelating residues (H202A/E204A) on a flexible loop, suggesting dynamic allosteric regulation of Rv0045c by divalent metals. Although serine hydrolases like Rv0045c are a large and diverse enzyme superfamily, this is the first structural confirmation of allosteric regulation of their enzymatic activity by divalent metals.
Take back the tweet: Social media use by anti‐gender‐based violence organizations
Authors: Stabile Bonnie , Grant Aubrey , Purohit Hemant , Sharan Bonala Sai
Published: April 2021

Social media can be a hostile environment for women, where threats of sexual assault and violence proliferate (Locke, Lawtom, and Lyons 2018; Jane 2014). Yet, social media sites like Twitter provide a platform for advocacy organizations seeking to influence public opinion and policy outcomes aimed at reducing gender‐based violence (GBV). Using anti‐GBV groups, this study follows research by Merry (2011, 2014) and Guo and Saxton (2018), to examine whether advocacy organizations effectively use Twitter to mobilize support and influence political communication and policy outcomes, where effectiveness is taken to be synonymous with more interactive communication. Interactivity among groups and the reach of their messaging (i.e., amount of attention received) are assessed to consider their effectiveness and potential mechanisms for broadening that reach. While empirical evidence of effectiveness based on the communicative quality of tweets is not advanced in this analysis, the quantity of tweets is affirmed as a mechanism of attention getting.
Immer wieder neu denken – Der Ingenieur und Hochschullehrer Stefan Polónyi † (1930–2021)
Authors: Bollinger Klaus , Hauke Bernhard , Kloft Harald
Published: April 2021

Der Ingenieur und Hochschullehrer Univ.‐Prof. em. Dr.‐Ing. E.h. mult. Stefan Polónyi ist am 9. April 2021 in Köln verstorben. Der nachfolgende Beitrag ist ein gekürztes Essay aus dem Jahrbuch Ingenieurbaukunst 2021. Dieser Beitrag erscheint auch in den Ernst & Sohn‐Zeitschriften Bautechnik Heft 5 und Beton‐ und Stahlbetonbau Heft 5.
A statistical analysis of the COHERENT data and applications to new physics
Authors: Denton Peter B. , Gehrlein Julia
Published: April 2021

Abstract

The observation of coherent elastic neutrino nucleus scattering (CEνNS) by the COHERENT collaboration in 2017 has opened a new window to both test Standard Model predictions at relatively low energies and probe new physics scenarios. Our investigations show, however, that a careful treatment of the statistical methods used to analyze the data is essential to derive correct constraints and bounds on new physics parameters. In this manuscript we perform a detailed analysis of the publicly available COHERENT CsI data making use of all available background data. We point out that Wilks’ theorem is not fulfilled in general and a calculation of the confidence regions via Monte Carlo simulations following a Feldman-Cousins procedure is necessary. As an example for the necessity of this approach to test new physics scenarios we quantify the allowed ranges for several scenarios with neutrino non-standard interactions. Furthermore, we provide accompanying code to enable an easy implementation of other new physics scenarios as well as data files of our results:https://github.com/JuliaGehrlein/7stats.
Super-Chern-Simons spectra from exceptional field theory
Authors: Varela Oscar
Published: April 2021

Abstract

Exceptional Field Theory has been recently shown to be very powerful to compute Kaluza-Klein spectra. Using these techniques, the mass matrix of Kaluza-Klein vector perturbations about a specific class of AdS4 solutions of D = 11 and massive type IIA supergravity is determined. These results are then employed to characterise the complete supersymmetric spectrum about some notable $$ \mathcal{N} $$
N
= 2 and $$ \mathcal{N} $$
N
= 3 AdS4 solutions in this class, which are dual to specific three-dimensional superconformal Chern-Simons field theories.
A Modified Tumor‐Node‐Metastasis Staging System for Colon Cancer Patients with Fewer than Twelve Lymph Nodes Examined
Authors: Zhang Hao , Liu Yunxiao , Wang Chunlin , Guan Zilong , Yu Hang , Xu Chao , Zheng Mingyu , Wang Yuliuming , Hu Hanqing , Huang Rui , Wang Guiyu
Published: April 2021

Background

To construct a modified tumor‐node‐metastasis (TNM) staging system for stage I‐III colon cancer patients with lymph nodes examined (LNE) < 12.

Methods

The clinicopathological and survival data of 3870 stage I‐III colon cancer patients with LNE < 12 from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015 (development cohort) and 126 stage I‐III patients with LNE < 12 from the Second Affiliated Hospital of Harbin Medical University between 2011 and 2015 (validation cohort) were identified. The optimal stratification of LNR for cancer‐specific survival (CSS) was achieved using X‐tile software. The predictive accuracy of the modified stage (mStage) was determined by the concordance index (C‐index).

Results

The modified N stage (mN stage) was built based on the LNR (mN0: LNR = 0, mN1: 0 < LNR < 0.4 or cancer nodule formation and mN2: 0.4 ≤ LNR ≤ 1). Preferable C‐indices could be found for mStage compared with TNM stage in both development (0.750 vs 0.727) and validation cohorts (0.682 vs 0.646). Besides, patients with mStage A and B diseases could not benefit from adjuvant chemotherapy, while in patients with mStage C‐F diseases, those receiving radical surgery plus adjuvant chemotherapy presented better CSS than those with radical surgery alone.

Conclusions

The mStage system could predict the prognosis of colon cancer patients with LNE < 12 accurately and showed superior predictive power compared with conventional TNM staging system. Moreover, adjuvant chemotherapy might play inequable roles in patients with different mStage diseases.
Explaining Siewierska’s generalization
Authors: Hallman Peter
Published: April 2021

This article presents an explanation for a cross-linguistic gap observed by Anna Siewierska: morphologically unmarked indirect objects may alternate with prepositional marking in what is sometimes called a ‘dative’ or ‘prepositional-dative’ ditransitive frame, but never with actual dative case marking. ‘Dative’, to the extent it alternates with accusative, is always expressed as a preposition. I show firstly that German, which has a robust dative case paradigm, also displays a double object alternation in which the erstwhile dative DP occurs in a prepositional phrase, meaning both accusative (in English) and dative (in German) indirect objects alternate with prepositional encoding. I construct an analysis in which the the indirect object may be generated as either a DP (which receives dative in German and accusative in English) or a PP in the same theta position. This characterization of the double object alternation does not admit an alternation between dative and accusative case on the indirect object, capturing Siewierska’s generalization. The analysis also extends to ‘symmetric’ passive languages, in which either object in the double object construction can be raised to subject in the passive. Some current perspectives on this phenomenon make such languages exceptions to Siewierska’s generalization, but not the analysis proposed here.
The prism model: advancing a theory of practice for arts and humanities in medical education
Authors: Moniz Tracy , Golafshani Maryam , Gaspar Carolyn M. , Adams Nancy E. , Haidet Paul , Sukhera Javeed , Volpe Rebecca L. , De Boer Claire , Lingard Lorelei
Published: April 2021

Introduction The arts and humanities have transformative potential for medical education. Realizing this potential requires an understanding of what arts and humanities teaching is and what it aims to do. A 2016 review of exclusively quantitative studies mapped three discursive positions (art as intrinsic to, additive to or curative for medicine) and three epistemic functions (art for mastering skills, perspective taking, and personal growth and activism). A more inclusive sample might offer new insights into the position and function of arts and humanities teaching in medical education.
Methods Informed by this 2016 framework, we conducted discursive and conceptual analyses of 769 citations from a database created in a recent scoping review. We also analyzed the 15 stakeholder interviews from this review for recurring themes. These three analyses were iteratively compared and combined to produce a model representing the complex relationship among discursive functions and learning domains.
Results The literature largely positioned arts and humanities as additive to medicine and focused on the functions of mastering skills and perspective taking. Stakeholders emphasized the intrinsic value of arts and humanities and advocated their utility for social critique and change. We offer a refined theory of practice—the Prism Model of four functions (mastering skills, perspective taking, personal insight and social advocacy)—to support more strategic use of arts and humanities in medical education across all learning domains.
Discussion The Prism Model encourages greater pedagogical flexibility and critical reflection in arts and humanities teaching, offering a foundation for achieving its transformative potential.
Structural distress: experiences of moral distress related to structural stigma during the COVID-19 pandemic
Authors: Sukhera Javeed , Kulkarni Chetana , Taylor Taryn
Published: April 2021

Introduction The COVID-19 pandemic has taken a significant toll on the health of structurally vulnerable patient populations as well as healthcare workers. The concepts of structural stigma and moral distress are important and interrelated, yet rarely explored or researched in medical education. Structural stigma refers to how discrimination towards certain groups is enacted through policy and practice. Moral distress describes the tension and conflict that health workers experience when they are unable to fulfil their duties due to circumstances outside of their control. In this study, the authors explored how resident physicians perceive moral distress in relation to structural stigma. An improved understanding of such experiences may provide insights into how to prepare future physicians to improve health equity.
Methods Utilizing constructivist grounded theory methodology, 22 participants from across Canada including 17 resident physicians from diverse specialties and 5 faculty members were recruited for semi-structured interviews from April–June 2020. Data were analyzed using constant comparative analysis.
Results Results describe a distinctive form of moral distress called structural distress, which centers upon the experience of powerlessness leading resident physicians to go above and beyond the call of duty, potentially worsening their psychological well-being. Faculty play a buffering role in mitigating the impact of structural distress by role modeling vulnerability and involving residents in policy decisions.
Conclusion These findings provide unique insights into teaching and learning about the care of structurally vulnerable populations and faculty’s role related to resident advocacy and decision-making.
LEVEL THEORY, PART 2: AXIOMATIZING THE BARE IDEA OF A POTENTIAL HIERARCHY
Authors: BUTTON TIM
Published: April 2021

Potentialists think that the concept of set is importantly modal. Using tensed language as a heuristic, the following bare-bones story introduces the idea of a potential hierarchy of sets: ‘Always: for any sets that existed, there is a set whose members are exactly those sets; there are no other sets’. Surprisingly, this story already guarantees well-foundedness and persistence. Moreover, if we assume that time is linear, the ensuing modal set theory is almost definitionally equivalent with non-modal set theories; specifically, with Level Theory, as developed in Part 1.
A Narrative Approach to Corporate Relations: The Historical Background on Telenor’s Success
Authors: CHRISTENSEN SVERRE A.
Published: April 2021

This article examines the development of buyer-supplier relations in the telecom sector. The literature on telecoms in Scandinavia has been dominated by the narrative praising the trusting and collaborative relations between Telia, the Swedish public telephone operator (PTO), and Ericsson, the equipment supplier. The Norwegian PTO, Telenor, diverted from this path and was a pioneer in preferring competitive tenders and arm’s length relations with its suppliers starting in the 1970s. The article argues that Telenor’s history and nationality had a significant impact on its business strategy. In addition, the article examines why some business narratives persist while others remain unknown. One finding is that shareholder-friendly narratives have a handicap because they focus on self-interest and money, and not societal values.
On uniqueness of invariant measures for random walks on
Authors: BROFFERIO SARA , BURACZEWSKI DARIUSZ , SZAREK TOMASZ
Published: April 2021

We consider random walks on the group of orientation-preserving homeomorphisms of the real line

${\mathbb R}$
. In particular, the fundamental question of uniqueness of an invariant measure of the generated process is raised. This problem was studied by Choquet and Deny [Sur l’équation de convolution

$\mu = \mu * \sigma $
. C. R. Acad. Sci. Paris250 (1960), 799–801] in the context of random walks generated by translations of the line. Nowadays the answer is quite well understood in general settings of strongly contractive systems. Here we focus on a broader class of systems satisfying the conditions of recurrence, contraction and unbounded action. We prove that under these conditions the random process possesses a unique invariant Radon measure on

${\mathbb R}$
. Our work can be viewed as following on from Babillot et al [The random difference equation

$X_n=A_n X_{n-1}+B_n$
in the critical case. Ann. Probab.25(1) (1997), 478–493] and Deroin et al [Symmetric random walk on

$\mathrm {HOMEO}^{+}(\mathbb {R})$
. Ann. Probab.41(3B) (2013), 2066–2089].
Rutherford, Privitera, and Chad Green: Laetrile’s Setbacks
in the Courts
Authors: Brant Jonathan , Graceffa John
Published: April 2021

The Chad Green case has again focused
national and international attention on the unproven cancer remedy known as
laetrile. Laetrile has attracted considerable attention in recent years as a
result of claims that it is a nontoxic form of cancer treatment. Twenty-one
states have legalized prescription of laetrile within their borders, despite
the efforts of the Food and Drug Administration (FDA) to keep laetrile off
the market.

The authors examine the claims about laetrile’s effectiveness and
comment upon scientific tests concerning its efficacy. They maintain that
scientific support for the use of laetrile is almost totally absent and that
evidence of the dangers of laetrile is substantial. After reviewing the
medical evidence concerning laetrile, the authors describe the efforts of
laetrile proponents to use the courts as the battleground to legalize
laetrile. In early skirmishes, laetrile proponents were successful in
opposing the efforts of the FDA; under a constitutional privacy theory
several courts upheld the right of competent adults to select laetrile
therapy.

Subsequently, however, as the authors demonstrate, the U.S. Supreme
Court, in United States v. Rutherford, and the
California Supreme Court, in People v. Privitera,
narrowed the federal constitutional privacy right by declining to read into
it a right to take laetrile. Finally, the Massachusetts Supreme Judicial
Court, in the Chad Green case, considered the
question of laetrile’s toxicity to a recipient of the drug.

The authors discuss the interrelationship among the three cases. They
argue that the overwhelming proof in Chad Green
that laetrile is harmful undermines any statutory or constitutional claims
supporting legalization, because such claims assume that even if laetrile is
not truly therapeutic outside of the placebo effect, it is not toxic. In
light of the three decisions, the authors conclude that supporters of
laetrile should not expect that the courts will be sympathetic to future
legal efforts to approve or to permit use of laetrile therapy.
Longitudinal associations between justice sensitivity, nonsuicidal self-injury, substance use, and victimization by peers
Authors: Bilgin Ayten , Bondü Rebecca , Elsner Birgit
Published: April 2021

Justice sensitivity (JS), the tendency to perceive and negatively respond to alleged injustice, has been associated with a range of internalizing and externalizing problems and peer victimization; however, it remains unclear if it has an association with self-victimization. Participants (N = 769) reported on their JS longitudinally at 9–19 (T1), 11–21 (T2), and 14–22 years of age (T3). They further reported on nonsuicidal self-injury (NSSI) and illegal substance use as indicators of self-victimization as well as victimization by peers at T2 and T3. A cross-lagged latent model revealed that victim JS at T1 was positively associated with NSSI, substance use, and peer victimization at T2, and victim JS at T2 was positively associated with substance use at T3. Higher observer JS at T2 predicted higher illegal substance use at T3 and higher illegal substance use at T2 predicted higher observer JS at T3. Finally, higher peer victimization at T2 predicted less perpetrator JS at T3 in the total group. Multigroup models further revealed sex-specific effects. Our findings highlight that being sensitive to injustice, particularly the tendency to feel unfairly treated or being taken advantage of, contributes to individuals’ vulnerability to both engaging in behaviors reflecting self-victimization and being a target of peer victimization, which in turn have influences on JS.
Additive bases via Fourier analysis
Authors: Arsovski Bodan
Published: April 2021

Extending a result by Alon, Linial, and Meshulam to abelian groups, we prove that if G is a finite abelian group of exponent m and S is a sequence of elements of G such that any subsequence of S consisting of at least
$$|S| - m\ln |G|$$
elements generates G, then S is an additive basis of G . We also prove that the additive span of any l generating sets of G contains a coset of a subgroup of size at least
$$|G{|^{1 - c{ \in ^l}}}$$
for certain c=c(m) and
$$ \in = \in (m) < 1$$
; we use the probabilistic method to give sharper values of c(m) and
$$ \in (m)$$
in the case when G is a vector space; and we give new proofs of related known results.
Perceptions of geographical indication labels as quality indicators inside and outside the labels’ area of influence: the case of spring fruits
Authors: Rabadán Adrián , Martínez-Carrasco Laura , Brugarolas Margarita , Bernabéu Rodolfo
Published: April 2021

Geographical indications (GIs) are valuable attributes that enhance the competitiveness of agri-food products, generate added value and revitalize rural environments. The aim of this work was to analyze the attributes spring fruit consumers associate with GIs when they decide to purchase these products. Moreover, the changes in these associations with the increasing distance between the region of production and the place of consumption were also evaluated. We specifically analyzed two GIs used for spring fruits: the protected geographical indication for Mountain Cherries from Alicante (Spain) and the protected designation of origin for Loquats from Callosa d'En Sarriá (Spain). Data were analyzed using logistic regression analysis. The results show the significant association in consumers' minds between the preference for GI fruit and the importance attributed to the place of production (origin). The association of different attributes with the GI fruit label is product dependent as the number of attributes associated in the case of cherries (origin, organic, color and variety) is higher than for loquats (origin and variety). Regarding the distance between the production area and the place of consumption, our findings suggest that the closer the consumer is to the GI area of influence, the more attributes they associate with these labels. In this regard, increasing the knowledge of the GI labels beyond their area of influence could boost the demand for these products as consumers would be aware of the different quality attributes concentrated in that label.