bluuebunny/crossref_metadata_2025 huggingface dataset:
On the Quantum‐Mechanical and Classical Treatment of Chemical Kinetics
Authors: Christov S. G.
Published: November 2023

In a recent quantum‐mechanical formulation of reaction rate theory the concept of a potential‐energy surface was used to derive an exact rate equation of the usual exponential form under the unique assumption of thermal equilibrium of reactants. In the present paper the notion of the “activated complex” is introduced in the sense of a virtual state to derive a mathematically equivalent expression of the same exponential form. This exact expression may be considered in a conditional sense as a generalization of “transition state theory”.

The classical limits of the exact quantum scattering theory are investigated for the extreme conditions of very slow (adiabatic) and very fast (non‐adiabatic) motion along the reaction coordinate using the two equivalent forms of the general rate equation, respectively. In this way two classical rate expressions are derived, one of which is identical with the familar Eyring's equation of transition state theory. The quantum corrections and, in particular, the “tunneling corrections” to these equations are defined exactly in a suitable manner and two corresponding simple criteria for determining the conditions of a classical reaction course are introduced.

Two‐dimensional quantum corrections for the colinear triatomic reaction H2 + H → H + H2 (D2 + D → D + D2) are calculated exactly using Weston's potential surface for the extreme conditions of both adiabatic and (truly) non‐adiabatic change of the vibration mode. A comparison is made with corresponding approximate formulas for the tunneling corrections. The activated complex hypothesis is shown to be not justified from physical point of view for reactions of the type AH + B → A + HB, where A and B are H, D, T or hypothetical super‐heavy hydrogen isotopes.

Finally, a discussion is made on the conditions of validity of the activated complex theory from physical standpoint and on its importance as a method for exact calculations of reaction rates which is shown to be largely independent from its physical justification.
Carrier‐Mediated Transport Across Black Lipid Membranes: Resistance of Spherical Films in the Presence of Derivates of Phenol and Benzoic Acid
Authors: Kübel Martin
Published: November 2023

Spherical membranes (area ≥ 1 cm2) of oxidized cholesterol are formed like soap bubbles and their electric resistance is measured in aqueous solutions, when the membrane has reached the “black” state (thickness ≅ 100 Å).

Experiments in physiology go to show that 2,4‐Dinitrophenol acts as uncoupler of oxidative phosphorylation and there exist theoretical models to explain this feature as well. It is shown that in contradiction to these models, phenol, salicylic acid, benzoic acid, and their amino derivates do not alter the transmembrane conductivity. But the conductivity increases linearly with the concentration of nitro derivates of these weak acids, and as more nitro groups are substituted into the molecules the stronger is their effect. This is independent of the nature of the membrane‐forming lipid. Neither the pK nor the molecular dipole moment can account for the effect of the nitrogroups. Therefore, one has to seek a chemical explanation.
Dielectric Relaxation of Water in Aqueous Solutions of n‐Alkylamine Hydrochlorides Part 1: Solute Concentrations Smaller than the Critical Micelle Concentrations
Authors: Kaatze U. , Limberg C. H. , Pottel R.
Published: November 2023

The solutes are the homologous salts CH3(CH2)nNH3Cl with n = 3, 5, 6, and 7. The complex permittivity of the solutions has been measured in dependence of frequency between 5 and 37 GHz at 25°C.

From the analysis of the frequency dependence of the complex permittivity, statements are made on the orientational polarizability, the reorientation time and the number of the hydration water molecules of the n‐alkylammonium ions. The orientational polarizability of the hydration water does not markedly differ from that of pure water. The reorientation time and the numbers of the disturbed water molecules around the cations strongly increase with increasing hydrocarbon chain length of the cations.

The reorientation times and the numbers of the hydration water molecules of the n‐alkylammonium ions are compared with those of the tetra‐alkylammonium ions. From this comparison is clearly established that the hydrophobic interaction around the former ions is more pronounced than around the latter.
Dielectric Relaxation of Water in Aqueous Solutions of n‐Alkylamine Hydrochlorides Part 2: Solute Concentrations Larger than the Critical Micelle Concentrations
Authors: Kaatze U. , Limberg C. H. , Pottel R.
Published: November 2023

The solutes are the chlorides of the amphiphilic cations CH3(CH2)n N+ H3 with n = 5, 6, 7, 9 and CH3(CH2)11 N+(CH3)3, which above the critical micelle concentration aggregate to micelles in aqueous solutions. The complex permittivity of the solutions has been measured in dependence of frequency between 5 and 37 GHz at 25°C.

From the analysis of the frequency dependence of the complex permittivity, statements are made on the micellar shape and on the microdynamics of the water molecules influenced by the micelles.

The micellar shape seems to be ellipsoidal within the high concentrated solutions. There are two species of micellar hydration water. One species is characterized by a very large reorientation time of the molecules. This effect is attributed to the pourous structure of the micellar surface. The reorientation time of the other species is somewhat smaller than the reorientation time of pure water. This is explained by weak electric fields acting near the micellar surface and thus causing negative hydration.
Die Temperaturabhängigkeit der Intensität der CH‐Valenzschwingungen von Benzolderivaten
Authors: Perkampus H.‐H. , Klampfer M.
Published: November 2023

Die Temperaturabhängigkeit der Intensität der CH‐Valenzschwingungen des Benzols und einiger Derivate, insbesondere der Methylbenzole, wurde in CCl4 als Lösungsmittel gemessen. Eine Bandenauftrennung mittels eines Computers ermöglichte es, die Intensität der aufgetrennten und mittels Normalkoordinatenanalyse zugeordneten Banden mit einer Genauigkeit von 12% zu bestimmen. Die Temperaturabhängigkeit der Intensität beträgt im Bereich von 283 bis 343 K 725% und läßt sich durch eine EDA‐Wechselwirkung mit dem Lösungsmittel erklären.
Beschreibung cholesterischer Mischsysteme mit einer erweiterten Goossens‐Theorie
Authors: Finkelmann H. , Stegemeyer H.
Published: November 2023

An einer Reihe von cholesterischen flüssig‐kristallinen Mischsystemen wurde die Abhängigkeit der “Helical twisting power” p−1 vom Molenbruch x gemessen, wobei die Art der Mischungskomponenten weitgehend variiert wurde. Zwei verschiedene Kurventypen p−1 (x) wurden beobachtet: a) lineare und b) nicht‐lineare mit einem Minimum. Im Fall b) traten zum Teil unerwartete Helixkompensationen auf Das beobachtete Verhalten läßt sich auf die verschiedene Molekülstruktur der Mischungskomponenten zurückführen. Die Ergebnisse werden anhand der früher [1,4] auf Mischungen erweiterten Goossens‐Theorie diskutiert und eine Unterteilung in “ideale” und “reale” cholesterische Mischsysteme vorgeschlagen.
Orientierung cholesterischer Mesophasen an mit Lecithin behandelten Oberflächen
Authors: Brehm M. , Finkelmann H. , Stegemeyer H.
Published: November 2023

Zwischen lecithin‐behandelten Glasoberflächen lassen sich cholesterische Mesophasen in dünnen Schichten ebenso wie nematische Flüssigkristalle homöotrop orientieren. Im Fall der cholesterischen Phasen muß aber das Lecithin vorher ein Aufspulen der Helix bewirkt haben. Das Nematisierungsvermögen des Lecithins wurde als Funktion der Temperatur, der Schichtdicke und der Zusammensetzung für verschiedene cholesterische Mischsysteme polarisationsmikroskopisch untersucht. Es ergab sich, daß eine cholesterische Mesophase durch Lecithin in eine homöotrope nematische bis zu Schichtdicken d0 in der Größenordnung einer Ganghöhe p umgewandelt werden kann.
Elastizität und Hydrodynamik flüssiger Kristalle
Authors: Helfrich W.
Published: November 2023

Es wird eine Übersicht über die Kontinuumsmechanik der flüssigen Kristalle gegeben, insbesondere über einige neuere Entwicklungen.
Leitfähigkeitsuntersuchungen am smektischen flüssigen Kristall 3‐[N‐(p‐Äthoxybenzyliden)‐amino]‐6‐n‐butylpyridin
Authors: Heppke G. , Schneider F.
Published: November 2023

Die elektrische Leitfähigkeit von 3‐[N‐(p‐Äthoxybenzyliden)‐amino]‐6‐n‐butylpyridin wird in der nematischen und den beiden smektischen Phasen in Abhängigkeit von der Temperatur untersucht. Während in der nematischen Phase die Leitfähigkeit parallel zum Direktor größer als senkrecht zu dieser Richtung ist, kehren sich die Verhältnisse in der smektischen Phase um. Bei der tiefsten Meßtemperatur von 20°C beträgt die Leitfähigkeit parallel zum Direktor nur 10% der Senkrechtleitfähigkeit.
Polyreaktionen in orientierten Systemen, 5*) Polyacryl‐ und ‐methacryl‐Schiffsche Basen mit flüssig‐kristallinen Eigenschaften
Authors: Perplies Eberhard , Ringsdorf Helmut , Wendorff Joachim H.
Published: November 2023

Flüssig‐kristalline Acryl‐ und Methacryl‐Schiffsche Basen wurden in Lösung und in der isotropen sowie anisotropen Schmelze polymerisiert. Die Eigenschaften der Polymeren wurden ermittelt und die Struktur der bei verschiedenen Bedingungen hergestellten Polymeren röntgeno‐graphisch untersucht. Die nematische Struktur der Monomeren geht bei der Polymerisation in eine smektische Struktur über. Während die polymeren Acrylester vernetzt waren, erwiesen sich die Polymethacrylester als unvernetzt. Sie zeigten typisch flüssig‐kristalline Strukturen und Eigenschaften.
EPR‐Spektren von Spin‐Labeln in Modell‐Membranen
Authors: Schindler Hansgeorg , Seelig Joachim
Published: November 2023

Verschiedene Spin‐Label (Fettsäurelabel, Steroidlabel) werden verwendet, um die Struktur und molekulare Bewegung in einer flüssig kristallinen Doppelschicht (Lipid Bilayer) zu untersuchen. Die EPR‐Spektren werden störungstheoretisch berechnet und computersimuliert. Die CH2‐Ketten zeigen eine schnelle anisotrope Bewegung. Die Rotationsdiffusion der Label um ihre Längsachsen ist R∥ ≈︁ 108/sec; die Rotationsdiffusion senkrecht zu dieser Achse R⊥ ≈︁ ist für die Steroidlabel R⊥ ≈︁ 108/sec. Die Viskosität der Phase liegt im Intervall 4,6 cp ≤ η 5,7 cp. Die Moleküle der Phase sind oberhalb von 20°C parallel zur Normalen der Doppelschicht orientiert; unterhalb von etwa 20°C zeigen die Label eine zunehmende Neigung der Kohlenwasserstoffketten bezüglich der Normalen an.
Deuterium‐magnetische Resonanzspektroskopie an spezifisch deuterierten flüssigen Kristallen
Authors: Niederberger Werner , Seelig Joachim
Published: November 2023

In einer lamellaren Phase aus Na‐Dekanoat, Dekanol und Wasser wurden die beiden Kohlenwasserstoffketten an verschiedenen Stellen spezifisch deuteriert. Mit Deuterium‐magnetischer Resonanzspektroskopie wurde der Ordnungsgrad der einzelnen Kettensegmente gemessen. Sein Wert ist über den größten Teil der Ketten konstant und fällt erst über die letzten 3–4 Kohlenstoffatome rasch ab. Dieses Resultat wird mit einem Modell erklärt, bei dem in den bevorzugt parallel orientierten Ketten ungefähr eine fluktuierende Kinke pro Kette auftritt, die sich an einer bestimmten Kettenstelle kürzer als 10−6 s aufhält.
Synthesis of a water‐stable CsPbBr3 perovskite for selective detection of mercury ion in water
Authors: Huang Jingtao , Hu Yi‐Lin , Liu Jin‐Zhou , Zhang Hai‐Chi , Cao Qiu‐E , Li Rong Sheng , Ling Jian
Published: November 2023

By using the method of low‐temperature crystallization, CsPbBr3 perovskite nanocrystals (PNCs) coated with trifluoroacetyl lysine (Tfa‐Lys) and oleamine (Olam) were synthesized in aqueous solution. The structure of the CsPbBr3 PNCs was characterized by many methods, such as ultraviolet (UV)‐visible absorption spectrophotometer, fluorescence spectrophotometer, transmission electron microscopy (TEM), and X‐ray diffraction (XRD) pattern. The fluorescence emission of the CsPbBr3 PNCs is stable in water for about 1 day at room temperature. It was also found that the fluorescence of the PNCs could be obviously and selectively quenched after the addition of mercury ion (Hg2+), allowing a visual detection of Hg2+ by the naked eye under UV light illumination. The fluorescence quenching rate (I0/I) has a good linear relationship with the addition of Hg2+ in the concentration range 0.075 to 1.5 mg/L, with a correlation coefficient (R2) of 0.997, and limit of detection of 0.046 mg/L. The fluorescence quenching mechanism of the PNCs was determined by the fluorescence lifetime and X‐ray photoelectron spectroscopy (XPS) of the PNCs. Overall, the synthesis method for CsPbBr3 PNCs is simple and rapid, and the as‐prepared PNCs are stable in water that could be conveniently used for selective detection of Hg2+ in the water environment.
One pot production of Co core/carbon shell materials and their electrocatalytic properties
Authors: Shin Yunseok , Park Sungjin
Published: November 2023

The oxygen reduction reaction (ORR) is a kinetically sluggish reaction because it requires the transfer of four electrons. In this work, one‐pot process involving thermal treatment of Co(II) acetylacetonate is developed. The resulting core–shell material (Co@C‐800) consists of metallic Co cores encapsulated by carbon‐based layered shells. Morphological analysis reveals the core–shell structures, with core particles surrounded by carbon networks. Chemical characterization using various spectroscopic techniques indicates the presence of metallic Co as the major component in Co@C‐800, with minor Co species exhibiting higher oxidation states. Raman spectroscopy confirms the formation of sp2‐hybridized carbon shells. Co@C‐800 displays efficient electrocatalytic ORR performance, evidenced by high onset and half‐wave potentials. The excellent durability and stability of Co@C‐800, demonstrated through resistance to methanol poisoning and cyclic testing, suggest the potential of core–shell materials as a practical electrocatalyst.
Chyluria secondary to disseminated tuberculosis in a 13‐year‐old female child: A case report
Authors: Bhatta Mukesh , Subedi Rejeena , Shah Abhishek , Baral Ranjita , Rauniyar Lalan Prasad , Shrestha Shishir , Ghimire Asha
Published: November 2023

Key Clinical Message

We report the case of chyluria secondary to disseminated tuberculosis in a 13‐year‐old female child who presented with passage of white colored urine since 5 months, progressive weight loss for 3 months, abdominal distension for 2 months, generalized swelling of body for 15 days, and pain in abdomen for 10 days. Child had good recovery following treatment with antitubercular drugs. Though chyluria is uncommon in children, tuberculosis could be considered as a differential, after ruling out filariasis.
Lipase mediated new chemo‐enzymatic synthesis of (RS)‐, (R)‐, and (S)‐bunolol
Authors: Patlolla Ravinder Reddy , Deepthi Pulivarthi , Raveena Gajjala , Rosangzuala Khawlhring , Tejaswini Somarowthu , Prakasham Reddy Shetty , Banoth Linga
Published: November 2023

The β‐adrenergic receptor blocking agents are an important class of drug molecules. The present study reports a new chemo and chemo‐enzymatic synthetic process for (RS)‐, (R)‐, and (S)‐bunolol, one of the potent β‐adrenergic receptor blocker. In chemo‐enzymatic process, CAL L4777 lipase was employed for enantioselective kinetic resolution to synthesize the enantiopure (R)‐alcohol and (S)‐ester from the corresponding racemic alcohol. Thereafter, the corresponding (R)‐alcohol and deacylated (S)‐ester were treated with tert‐butylamine to produce (S)‐ and (R)‐bunolol, respectively. In chemical approach, epichlorohydrin (RS‐, R‐, and S‐) was used as a starting material via respective (RS)‐, (S)‐, and (R)‐glycidyl ether as intermediates for synthesis of enantiomeric (RS)‐, (R)‐, and (S)‐bunolol. In comparison between two approaches, it was found that the chemo‐enzymatic process was more effective and resulted in enantiomeric excess of 98% with 35% yield.
Theoretical study of the interaction between the antibiotic linezolid and the active site of the 50S ribosomal subunit of the bacterium Haloarcula marismortui
Authors: Grandini Giulia Saneti , Morgon Nelson Henrique , de Souza Aguinaldo Robinson
Published: November 2023

First antibiotic in the oxazolidinone class, linezolid fights gram‐positive multiresistant bacteria by inhibiting protein synthesis through its interaction with the 50S subunit of the functional bacterial ribosome. For its antimicrobial action, it is necessary that its chiral carbon located in the oxazolidinone ring is in the S‐conformation. Computational calculation at time‐dependent density functional theory methodology, ultraviolet–visible (UV–Vis), and electronic circular dichroism spectra was obtained for noncomplexed and complexed forms of linezolid to verify the possible chirality of nitrogen atom in the acetamide group of the molecule. The molecular system has two chiral centers. So, there are now four possible configurations: RR, RS, SR, and SS. For a better understanding of the system, the electronic spectra at the PBE0/6‐311++G(3df,2p) level of theory were obtained. The complexed form was obtained from the crystallographic data of the ribosome, containing the S‐linezolid molecular system. The computational results obtained for the electronic properties are in good agreement with the experimental crystallographic data and available theoretical results.
Chemotherapy and adjuvant therapies' impact on the internal remodeling process of bone and its mechanical behavior for breast cancer patients
Authors: Ait Oumghar Imane , Barkaoui Abdelwahed , Merzouki Tarek , Guenoun Daphne , Chabrand Patrick
Published: November 2023

Breast cancer is a significant public health issue affecting women worldwide. While advancements in treatment options have led to improved survival rates, the impact of breast cancer and its treatments on bone health cannot be overlooked. Bone remodeling is a complex process regulated by the delicate balance between bone formation and resorption. Any disruption to this balance can lead to decreased bone density, increased fracture risk, and compromised physical function. To investigate the effects of breast cancer and its treatments on bone remodeling, a finite element model was developed in this study. This model incorporated bone remodeling equations to simulate the mechanical behavior of bone under different conditions. The ABAQUS/UMAT software was used to simulate the behavior of bone tissue under the influence of breast cancer and treatments. Our findings suggest that bone loss is more pronounced after secondary breast cancer and treatment, leading to bone loss (6%–19% decrease in BV/TV), reduced bone stimulation, and decreased effectiveness of physical activity on recovery. These results highlight the importance of early intervention and management of bone health in breast cancer patients to mitigate the negative impact of cancer and treatment on bone remodeling.
HIF‐1α‐inhibited Nanophotosensitizers for Near‐infrared Fluorescence Imaging‐guided Enhanced Photodynamic Therapy
Authors: Yin Likun , Zhang Xi , Diao Shanchao , Liu Yaxin , Gu Xuxuan , Zhou Wen , Xie Chen , Fan Quli
Published: November 2023

Photodynamic therapy (PDT) holds great potential in cancer therapy by virtue of its high precision, non‐invasiveness and low side effect. However, the hypoxic environment of solid tumor significantly restricts the efficacy of PDT. To improve the hypoxic microenvironment, inhibiting the hypoxia‐inducible factor 1α (HIF‐1α) is a rational approach. However, the related small molecule inhibitors suffer from the issue of poor tumor targeting. Herein, we design a nanophotosensitizer AmPPa NP which can inhibit HIF‐1α and conduct PDT with improved efficacy. AmPPa NP is prepared by first encapsulating a hydrophobic NIR photosensitizer mPPa into a carboxyl‐rich amphiphilic copolymer PSMA‐PEG, and then loading a positively charged HIF‐1α inhibitor acriflavine (ACF) on the surface of nanoparticle via electrostatic interaction. Under 635 nm laser irradiation, mPPa within nanoparticles can not only generate 1O2 for PDT but also emit NIR fluorescence signal for tumor imaging. In addition, such design makes ACF can be selectively released under acidic tumor microenvironment. Compared with mPPa NP without ACF loading, AmPPa NP can effectively inhibit HIF‐1α and shows improved PDT efficacy both in vitro and in vivo. This study thus provides a nanotheranostic platform for NIR fluorescence imaging‐guided enhanced PDT.
The Effect of BI 730357 (Retinoic Acid‐Related Orphan Receptor Gamma t Antagonist, Bevurogant) on the Pharmacokinetics of a Transporter Probe Cocktail, Including Digoxin, Furosemide, Metformin, and Rosuvastatin: An Open‐Label, Non‐randomized, 2‐Period Fixed‐Sequence Trial in Healthy Subjects
Authors: Choi HeeJae , Huang Fenglei , Flack Mary
Published: November 2023

Evaluating Drug‐Drug Interactions (DDIs) for new investigational compounds requires several trials evaluating different drugs with different transporter specificities. By using a cocktail of drugs with different transporter specificities, a single trial could evaluate the pharmacokinetics (PKs) of each cocktail drug simultaneously, reducing the number of clinical DDI trials required for clinical development. We aimed to investigate the effect of steady‐state Boehringer Ingelheim (BI) 730357 (bevurogant) on the PKs of a validated and optimized 4‐component transporter cocktail. This open‐label, non‐randomized, 2‐period fixed‐sequence phase I trial compared transporter cocktail (0.25 mg digoxin/1 mg furosemide/10 mg metformin hydrochloride/10 mg rosuvastatin) with and without BI 730357 in healthy subjects aged 18‐55 years with body mass index 18.5‐29.9 kg/m2. During reference treatment/period 1, transporter cocktail was administered 90 minutes after breakfast. After a washout period, during test treatment/period 2, BI 730357 was dosed twice daily for 13 days, with transporter cocktail administered on day 1. The primary endpoints were the area under the concentration‐time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0‐∞) and the maximum measured concentration of the analyte in plasma (Cmax), and the secondary endpoint was the area under the concentration‐time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point (AUC0‐tz). Steady‐state BI 730357 increased digoxin (+48% to +94%), minimally affected metformin (−2% to −9%), furosemide (+12% to +18%), and rosuvastatin (+19% to +39%) exposure. Therefore, no clinically relevant inhibition of transporters OCT2/MATE‐1/MATE‐2K, OAT1/OAT3, OATP1B1/OATP1B3 was observed. Potential inhibition of breast cancer resistance protein noted as PK parameters of coproporphyrin I/III (OATP1B1/OATP1B3 biomarkers) remained within bioequivalence boundaries while rosuvastatin PK parameters (AUC0‐∞/Cmax/AUC0‐tz) exceeded the bioequivalence boundary. BI 730357 was safe and well tolerated. This trial confirms the usefulness and tolerability of the transporter cocktail consisting of digoxin, furosemide, metformin, and rosuvastatin in assessing drug‐transporter interactions in vivo.
A randomized, double‐blind phase 1b study evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics of the NLRP3 inhibitor selnoflast in patients with moderate to severe active ulcerative colitis
Authors: Klughammer Barbara , Piali Luca , Nica Alexandra , Nagel Sandra , Bailey Lorna , Jochum Christoph , Ignatenko Stanislav , Bläuer Angela , Danilin Sabrina , Gulati Pratiksha , Hayward Joanne , Scepanovic Petar , Zhang Jitao David , Bhosale Satish , Chong Chui Fung , Christ Andreas
Published: November 2023

Background

The NLRP3 inflammasome drives release of pro‐inflammatory cytokines including interleukin (IL)‐1β and IL‐18 and is a potential target for ulcerative colitis (UC). Selnoflast (RO7486967) is an orally active, potent, selective and reversible small molecule NLRP3 inhibitor. We conducted a randomized, placebo‐controlled Phase 1b study to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of selnoflast.

Methods

Nineteen adults with previous diagnosis of UC and current active moderate to severe disease were randomized 2:1 to selnoflast or placebo for 7 days. A dose of 450 mg QD (once daily) was selected to achieve 90% IL‐1β inhibition in plasma and colon tissue. Consecutive blood, sigmoid colon biopsies and stool samples were analyzed for a variety of PD markers. Safety and PK were also evaluated.

Results

Selnoflast was well‐tolerated. Plasma concentrations increased rapidly after oral administration, reaching Tmax 1 h post‐dose. Mean plasma concentrations stayed above the IL‐1β IC90 level throughout the dosing interval (mean Ctrough on Day 1 and Day 5: 2.55 μg/mL and 2.66 μg/mL, respectively). At steady state, post‐dose selnoflast concentrations in sigmoid colon (5‐20 μg/g) were above the IC90. Production of IL‐1β was reduced in whole blood following ex vivo stimulation with lipopolysaccharide (LPS) (in the selnoflast arm). No changes were observed in plasma IL‐18 levels. There were no meaningful differences in the expression of an IL‐1‐related gene signature in sigmoid colon tissue, and no differences in the expression of stool biomarkers.

Conclusions

Selnoflast was safe and well‐tolerated. Selnoflast 450 mg QD achieved plasma and tissue exposure predicted to maintain IL‐1β IC90 over the dosing interval. However, PD biomarker results showed no robust differences between treatment arms, suggesting no major therapeutic effects are to be expected in UC. The limitations of this study are its small sample size and indirect assessment of the effect on IL‐1β in tissue.

Trial registration

ISRCTN16847938
Catalytic Water Oxidation by Ruthenium Complexes with Pyridine Alkoxide Ligands
Authors: Song Dan , Chen Jing , Wang Rui , Guo Zhenguo , Xie Jianhui , Liu Yingying
Published: November 2023

Ligand design is crucial for the design of robust and efficient molecular water oxidation catalysts (WOCs) based on metal complexes. Herein we report the water oxidation studies of a series of Ru WOCs bearing bipyridine dialkoxide ligands with different substituents. Combined with density functional theory (DFT) calculations, the proposed water oxidation mechanism is bimolecular coupling (I2M) of two seven‐coordinate (CN7) Ru=O species. The use of bulky phenyl groups on the planar alkoxide ligand helps to stabilize the high oxidation CN7 intermediates, without loss of ligand flexibility. This strategy may be useful for the design of other active WOCs.
Computational Studies on the Tropylium‐Catalyzed Carboxylic Acid O−H Insertion with Diazoesters: The Role of Homoaromaticity**
Authors: Anoop Anakuthil , Ganesh Venkataraman
Published: November 2023

A tropylium‐catalyzed carboxylic acid O−H insertion with diazoesters was reported to provide α‐hydroxy esters through an activated carbene intermediate. This study presents a revised mechanism based on density functional theory (DFT) calculations involving a unique homoaromatic intermediate formed between the tropylium ion and the diazoester. The calculated energies of the intermediates and transition states support this revised mechanism. Our computational model explains the tropylium ion‘s binding to the diazoester, resulting in the homoaromatic intermediate. By comparing the reaction profiles of four different pathways, our findings contribute to a better understanding of the reaction mechanism and have potential implications for designing more efficient catalytic systems.
Synthesis of Densely Substituted Pyridines through 1,2‐Oxazine‐6‐ones Inverse Electron Demand Diels–Alder Reaction
Authors: Ivanov Dmitrii S. , Smirnov Alexander Yu. , Zaitseva Elvira R. , Mikhaylov Andrey A. , Baranov Mikhail S.
Published: November 2023

Densely substituted pyridines are synthesized from available 1,2‐oxazin‐6‐ones and enamines through tandem hetero‐Diels–Alder and retro‐Diels–Alder reaction in 45–98 % yield.
Structural control of nickel nanowire arrays for use as non‐enzymatic glucose sensors
Authors: Shey Nicholas H. , Margetts Rebecca M. , Gillette Eleanor I.
Published: November 2023

A series of non‐enzymatic electrochemical glucose sensors were prepared by template‐assisted electrodeposition of nickel to produce nickel nanowire arrays (NiNWAs) of varying lengths. These electrodes were analyzed for their performance as non‐enzymatic glucose sensors, in order to explore the relationship between nanowire structure and electrochemical sensor performance. All of the NiNWAs, regardless of length, had linear responses to glucose in the 0.05–10 mM range. However, an inverse relationship between wire length and sensitivity was observed: the shortest of the NiNWAs had a sensitivity of 160 μA mM−1 cm−2, while the longest NiNWA had a sensitivity of only 100 μA mM−1 cm−2. This indicates that, with no other change to material parameters, choosing an optimum length of nanowire provides significant improvement in performance. No change in electrochemical mechanism was observed by cyclic voltammetry, and no significant loss of selectivity was observed with varying nanowire length. This study demonstrates that the structural optimization of an electrode can provide significant performance enhancement for nickel‐based electrochemical sensors.
Enrichment characteristics and exploration potential of the Permian marine shale gas in the Wujiaping Formation, Sichuan Basin, SW China
Authors: Nie Haikuan , Li Pei , Ding Jianghui
Published: November 2023

Shale gas exploration has achieved global success in marine shales. This study analysed geochemical, mineralogical, porosity, permeability and gas‐bearing parameters of organic‐rich shales in the Permian Wujiaping Formation in the Sichuan Basin. A comprehensive comparison was conducted with the Longtan Formation transitional shales and typical commercially developed marine shales. The results showed that: (1) siliceous shale within the Wujiaping Formation exhibits total organic carbon content ranging from 0.60% to 9.53% (average 4.45%) and vitrinite reflectance (Ro) ranging from 1.83% to 2.14% (average 1.98%), indicating an overmature stage of hydrocarbon generation. Porosity varies from 0.48% to 11.8% (average 4.94%), with an average content of 51.4% brittle minerals (quartz+calcite+dolomite) and calculating gas content exceeding 3 m3/t based on logging data. Effective sealing is achieved by the overlying carbonate of the Changxing Formation and the underlying carbonate of the Maokou Formation. (2) The primary storage space of the siliceous shale in the Wujiaping Formation encompasses diverse organic matter pores, clay mineral pores and microfractures. The porosity and permeability of the Wujiaping Formation marine shale ranges from 0.48% to 11.8% and 0.0053 to 0.8450 mD. Total gas content was estimated between 3 to 12 m3/t averaging 6 m3/t. (3) By comparing Permian Wujiaping Formation shales with Longtan Formation transitional shales, Wufeng Formation‐Longmaxi Formation shales and the typical North American marine gas shales (such as Barnett, Ohio, Antrim, New Albany, etc.), we conclude that marine siliceous shales within the Wujiaping Formation exhibit enrichment conditions comparable to established marine shales and superior to Permian transitional shales. The favourable upper and lower seals of the Wujiaping Formation resemble those of the Barnett shale gas reservoirs. In conclusion, the marine shale in Wujiaping Formation holds potential for substantial shale gas reservoirs and is poised for strategic exploration and development breakthroughs in the northeast and east Sichuan Basin.
Past: Imperfect; Future: Tense
Authors: Wynia Matthew K.
Published: November 2023

How should the field of bioethics grapple with a history that includes ethicists who supported eugenics, scientific racism, and even Nazi medicine and also ethicists who created the salutary policy and practice responses to those heinous aspects of medical history? Learning humility from studying historical errors is one path to improvement; finding courage from studying historical strengths is another, but these can be in tension. This commentary lays out these paths and seeks to apply them both to a contemporary challenge facing the field: why hasn't bioethics been more at the forefront of efforts to address inequities in health and health care?
Trust in Health Care and Science: Toward Common Ground on Key Concepts
Authors: Taylor Lauren A. , Solomon Mildred Z. , Kaebnick Gregory E.
Published: November 2023

This essay summarizes key insights across the essays in the Hastings Center Report's special report “Time to Rebuild: Essays on Trust in Health Care and Science.” These insights concern trust and trustworthiness as distinct concepts, competence as a necessary but not sufficient input to trust, trust as a reciprocal good, trust as an interpersonal as well as structural phenomena, the ethical impermissibility of seeking to win trust without being trustworthy, building and borrowing trust as distinct strategies, and challenges to trustworthiness posed by the contingent nature of science. Together, these insights stand to advance an area of research that we believe has been historically stymied by conceptual confusion and a long‐standing insistence on treating trust as a purely instrumental good.
Hippocampal TMEM55B overexpression in the 5XFAD mouse model of Alzheimer's disease
Authors: Odfalk Kristian F. , Wickline Jessica L. , Smith Sabrina , Dobrowolski Radek , Hopp Sarah C.
Published: November 2023

Dysfunction of the endosomal‐lysosomal network is a notable feature of Alzheimer's disease (AD) pathology. Dysfunctional endo‐lysosomal vacuoles accumulate in dystrophic neurites surrounding amyloid β (Aβ) plaques and may be involved in the pathogenesis and progression of Aβ aggregates. Trafficking and thus maturation of these dysfunctional vacuoles is disrupted in the vicinity of Aβ plaques. Transmembrane protein 55B (TMEM55B), also known as phosphatidylinositol‐4,5‐bisphosphate 4‐phosphatase 1 (PIP4P1) is an endo‐lysosomal membrane protein that is necessary for appropriate trafficking of endo‐lysosomes. The present study tested whether overexpression of TMEM55B in the hippocampus could prevent plaque‐associated axonal accumulation of dysfunctional endo‐lysosomes, reduce Aβ plaque load, and prevent hippocampal‐dependent learning and memory deficits in the 5XFAD mouse models of Aβ plaque pathology. Immunohistochemical analyses revealed a modest but significant reduction in the accumulation of endo‐lysosomes in dystrophic neurites surrounding Aβ plaques, but there was no change in hippocampal‐dependent memory or plaque load. Overall, these data indicate a potential role for TMEM55B in reducing endo‐lysosomal dysfunction during AD‐like Aβ pathology.
Synthesis and Olfactory Properties of Lower‐Ring Homologues of the Linear Alicyclic Musk Romandolide
Authors: Dacho Vladimír , Nikipelov Artem , Tóthová Michaela , Kraft Philip , Szolcsányi Peter
Published: November 2023

In order to expand the knowledge on linear alicyclic musks, a set of 29 small‐ring (racemic) analogues of the biodegradable and renewable alicyclic musk Romandolide was designed, prepared, and evaluated. The common short and modular synthesis employs either commercially available or easily accessible (substituted) cyclopropyl/cyclobutyl ketones and acids. These were transformed in three/four steps to the target compounds. Their qualitative olfactory analysis reveals that contraction of cyclohexane ring of Romandolide to smaller rings annihilates the genuine musk scent, though many of these share the metallic hot‐iron off‐note of some macrocyclic musks. Indeed, these new derivatives exhibit a plethora of pleasant, interesting, and potentially useful scents including herbal, green, fruity, or chocolate ones accompanied by various undertones. The powdery, fruity ionone odor of the dimethyl cyclobutyl compound was found to be most interesting as it possesses a very natural raspberry and violet character. Computational modelling suggest that the lowest‐energy conformers of the target compounds do either not adopt a true U‐shape as was speculated to be a prerequisite for a musk odor, or that the quaternary carbon atom of the dimethyl‐substituted cyclobutane is not well placed to fit into a hydrophobic binding pocket on the corresponding receptor site.
Young graduates and economic recession: Lessons from the pandemic to prevent the (re)incidence of mental health symptoms
Authors: Suleman Fátima , Carvalho Diana
Published: November 2023

Economic conditions affect the youth labour market and can leave deep scars. This exploratory study examines the emotional responses and mental health symptoms of young graduates during their transition into the labour market in the pandemic context. It draws on 42 news articles with statements from 86 graduates from a set of European and non‐European countries. The graduates had jobs or internships cancelled, numerous applications unanswered or were dismissed from jobs they had recently started. Young people adopt a variety of coping strategies, which are often invisible and cause deep suffering due to anxiety, disappointment, fear, and depression. Their apprehension and uncertainty leave them in a state of limbo. The specific impacts of the pandemic on young people's lives serve as a warning of the need to protect future generations of graduates. More support is required worldwide to manage the mental health issues that affect young graduates, especially during economic recessions.
Access and barriers to genomic classifiers for breast cancer and prostate cancer in India
Authors: Ranganathan Sruthi , Dee Edward Christopher , Debnath Neha , Patel Tej A. , Jain Bhav , Murthy Vedang
Published: November 2023

The incidence of cancer in general, including breast and prostate cancer specifically, is increasing in India. Breast and prostate cancers have genomic classifiers developed to guide therapy decisions. However, these genomic classifiers are often inaccessible in India due to high cost. These classifiers may also be less suitable to the Indian population, as data primarily from patients in wealthy Western countries were used in developing these genomic classifiers. In addition to the limitations in using these existing genomic classifiers, developing and validating new genomic classifiers for breast and prostate cancer in India is challenging due to the heterogeneity in the Indian population. However, there are steps that can be taken to address the various barriers that currently exist for accurate, accessible genomic classifiers for cancer in India.
Long‐term effects of surgically corrected menstrual outflow obstruction: A case–control study
Authors: Martens Lisanne , Spath Marian A. , van Beek Monique A. , Willemsen Wim N. P. , Kluivers Kirsten B.
Published: November 2023

Objective

To enhance evidence‐based knowledge on long‐term sequalae in patients with surgically corrected obstructing Müllerian anomalies.

Methods

This long‐term case–control study included patients with menstrual outflow obstruction due to congenital anomalies of the uterus or vagina, who were at least 18 years old, and for whom 2 years had elapsed since the first surgery at the start of this study. The control group consisted of women without current gynecological problems. Patients underwent a surgical correction at the Radboud University Medical Center Nijmegen between 1980 and 2013. Of 78 patients approached, 38 (49%) were included in this study. The control group consisted of 54 females. The main outcome measures were pain and health state. The following questionnaires were used: Visual Analogue Scale pain scores, European Quality of Life–5 Dimensions questionnaire (EQ‐5D‐3L) and the adapted Endometriosis Health Profile questionnaire (EHP‐30).

Results

Patients had higher actual and maximum abdominal pain scores compared with controls (11 vs 0 [P = 0.007] and 48 vs 21 [P = 0.035], respectively). Based on the EQ‐5D‐3L scores, patients had more pain and discomfort (P = 0.005), more mood problems (P = 0.023), and a poorer subjective health state (P = 0.002) and self‐rated health state (P = 0.031). Based on the EHP‐30, patients had a significant poorer self‐rated health state on four out of five subscales.

Conclusion

In this study, following surgically corrected menstrual obstruction, patients had statistically significant higher abdominal pain scores and a poorer self‐rated health state compared with controls.
Aggravation of cognitive impairments in the valproic acid‐induced animal model of autism in BALB/c mice infected with Toxoplasma gondii
Authors: Sheikhshoaee Saeed , Taheri Farahnaz , Esmaeilpour Khadijeh , Firouzeh Nima , Fard Saeid Reza Nourollahi
Published: November 2023

Purpose

Toxoplasmosis is a disease caused by infection with a type of coccidial protozoan parasite called Toxoplasma gondii. The relationship between toxoplasmosis and cognitive disorders in neurodegenerative diseases has been proven. There is also evidence that children born to Toxoplasma‐infected mothers are more likely to develop autism.

Methods

In the present study, Toxoplasma‐infected pregnant BALB/c mice were given valproic acid to induce autism in their male offspring, and their social behaviors, learning, and memory were examined. Chronic toxoplasmosis was established in BALB/c mice by intraperitoneal injection of cyst form of T. gondii. To induce autism, 600 mg/kg of valproic acid was injected intraperitoneally into mice on the 12.5th day of pregnancy. The behavioral experiments, such as social interaction, novel object recognition, and passive avoidance tasks, were performed on male offspring at 50 days.

Results

Toxoplasma and valproic acid during the embryonic period caused social communication deficits and disrupted recognition memory and avoidance memory in offspring. Our findings showed that administering valproic acid to Toxoplasma‐infected mothers exacerbates cognitive disorders in their offspring.
Examining interactions between dominant discourses and engineering educational concepts in teachers' pedagogical reasoning
Authors: De Lucca Natalie , Watkins Jessica , Swanson Rebecca D. , Portsmore Merredith
Published: November 2023

Background

Engineering's introduction into K–12 classrooms has been purported to support meaningful and inclusive learning environments. However, teachers must contend with dominant discourses embedded in US schooling that justify inequitable distributions of resources.

Purpose

Drawing on Gee's notion of discourses, we examine how teachers incorporate language legitimizing socially and culturally constructed values and beliefs. In particular, we focus on the discourse of ability hierarchy—reflecting dominant values of sorting and ranking students based on perceived academic abilities—and the discourse of individual blame—reflecting dominant framings of educational problems as solely the responsibility of individual students or families. We aim to understand how these discourses surface in teachers' reasoning about teaching engineering.

Method

We interviewed 15 teachers enrolled in an online graduate program in engineering education. Utilizing critical discourse analysis, we analyzed how teachers drew on discourses of blame and ability hierarchy when reasoning about problems of practice in engineering.

Results

Teachers drew on engineering education concepts to reinforce dominant discourses (echoing specific language and preserving given roles) as well as to disrupt (utilizing different language or roles that [implicitly] challenge) dominant discourses. Importantly, teachers could also retool discourses of ability hierarchy (arguing for a more equitable distribution of resources but problematically preserving the values of ranking and sorting students).

Conclusions

K–12 schooling's sociohistorical context can shape how teachers make sense of engineering in ways that implicate race, gender, disability, and language, suggesting a need to grapple with how discourses from schooling—and engineering culture—maintain marginalizing environments for students.
How Bad Leaders Can Drive Out Good Leaders
Authors: Emblemsvåg Marianne Synnes , Emblemsvåg Jan
Published: November 2023

Destructive leadership has been thoroughly described in the literature. As the term itself indicates, destructive leadership is a leadership style that violates the well‐being or job satisfaction of subordinates, and destroys value for the organization directly, or through less motivated and effective employees. Despite such negative effects, some members might prosper from it and may even support destructive leadership. Worse, sometimes destructive leaders are promoted. If the organization rewards destructive leaders with promotions and responsibility, followers may see these behaviors as a way to get ahead and destructive behavior can become a part of the organizational culture. The literature still reports increased turnover intentions. In the current article, the consequences of destructive leadership on leaders and followers are examined. Specifically, destructive leadership is examined through a literature review and by using Gresham's law as an analogy. Gresham's law states that “bad money drives out good money,” and the current article demonstrates that a Gresham‐tendency can also be observed for leaders under certain circumstances. Thus, the current study converts Gresham's law into a conceptual model for the evolution of destructive leadership in organizations. The proposed model qualitatively describes how various types of destructive leaders influence the organization under certain circumstances.
Common traits in online shopping behavior: A study of different generational cohorts
Authors: Nwobodo Stanley , Weissmann Marc Arul
Published: November 2023

This study examines the online shopping behavior of the different generational cohorts (X, Y, and Z) to determine the differences and similarities in their behavioral patterns. The study's findings in the Malaysian context reveal that, irrespective of generational cohorts, key factors significantly influence online shopping behavior. Notably, information quality and source credibility play a pivotal role in enhancing information usefulness, highlighting consumers' strong emphasis on the credibility and quality of information sources when making online purchase decisions. Additionally, personalized services provided by online retailers positively influence consumers' habitual behavior, reduce their willingness to switch to other retailers, and encourage online purchases. This suggests that tailored services and products catering to individual needs foster repeat behavior and customer loyalty. Interestingly, generational cohorts appear to have little impact on consumer responses, indicating that, as online shopping becomes more prevalent, consumer behavior tends to align around common traits, such as valuing information quality and credibility, personalized services, and the formation of positive shopping habits.