bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of Intraperitoneal Tumor Growth of Human Ovarian Cancer Cells by Bi- and Trifunctional Inhibitors of Tumor-Associated Proteolytic Systems
Authors: Krol J. , Kopitz C. , Kirschenhofer A. , Schmitt M. , Magdolen U. , Krüger A. , Magdolen V.
Published: September 2004

Several proteolytic systems are involved in (anti)adhesive, migratory, and proteolytic processes, necessary for tumor progression and metastasis. We analyzed whether multifunctional inhibitors of different tumor-associated proteolytic systems reduce tumor growth and spread of human ovarian cancer cells in vivo. Bifunctional inhibitors are composed of the N-terminal domain of either the human matrix metalloproteinase inhibitors TIMP-1 or TIMP-3 and the cysteine protease inhibitor chicken cystatin (chCysWT); trifunctional inhibitors are composed of N-TIMP-1 or -3 and a chicken cystatin variant harboring the uPAR binding site of uPA, chCys-uPA19-31, which in addition to its inhibitory activity toward cysteine proteases interferes with the interaction of the serine protease uPA with its receptor. OV-MZ-6#8 cancer cells, stably transfected with plasmids expressing the multifunctional inhibitors, displayed similar proliferative and adhesive features as the vector-transfected control, but showed significant reduction in their invasive behavior in vitro. The cell lines expressing the multifunctional inhibitors were inoculated into the peritoneum of nude mice. Expression of three of the four inhibitor variants (NhTIMP-1-chCysWT, N-hTIMP-1- chCys-uPA19-31, and N-hTIMP-3-chCysWT) resulted in a significant reduction of tumor burden compared to the vector-control cell line. These compact and small inhibitors may represent promising agents for gene therapy of solid malignant tumors.
Assignment of Disulphide Bridges in Par j 2.0101, a Major Allergen of Parietaria judaica Pollen
Authors: Amoresano A. , Pucci P. , Duro G. , Colombo P. , Costa M. A. , Izzo V. , Lamba D. , Geraci D.
Published: September 2004

Par j 2.0101, a major allergen of the Parietaria judaica pollen, was expressed in E. coli, purified to homogeneity and fully characterised both at the structural and the functional level. The recombinant rPar j 2.0101 protein showed an allergenic activity in histamine release, skin prick tests and capacity to bind IgE, almost identical to that of the native allergens purified from aqueous pollen extract. The complete pattern of S-S bridges of rPar j 2.0101 was determined by enzymatic digestion with endoproteinase Lys-C followed by mass spectrometric analysis of the resulting peptide mixtures. The eight cysteines occurring in the allergenic protein were found to be paired into the following four disulphides: Cys35-Cys83, Cys45- Cys60, Cys61-Cys106 and Cys81-Cys121. This structural information probes Par j 2.0101 to attain a 3-D fold consistent with that of the nonspecific lipid transfer protein (ns-LTP) family and it represents an effective molecular basis to develop modified antigens by selective site-directed mutagenesis for immunotherapy.
The Activator-Binding Site of Onchocerca volvulus S-Adenosylmethionine Decarboxylase, a Potential Drug Target
Authors: Ndjonka D. , Zou Y. , Bi X. , Woster P. , Walter R. D. , Lüersen K.
Published: September 2004

S-Adenosylmethionine decarboxylase (AdoMetDC) is a key enzyme in polyamine biosynthesis. In many eukaryotes its activity is stimulated specifically by putrescine. The AdoMetDC of the filarial parasite Onchocerca volvulus, however, is not only stimulated by putrescine but also by the naturally occuring polyamines spermidine and spermine. Several diamines, acetylated polyamines and polyamine analogues were used to analyse what molecular prerequisites are needed to stimulate nematode AdoMetDC activity. In the absence of an activator, the O. volvulus enzyme exhibits an extremely low specific activity. This fact, together with the unspecificity of activator binding, was thought to be useful for a new strategy to inhibit nematode AdoMetDC activity. Therefore, different polyamine analogues were tested as competitive inhibitors towards the stimulatory effect putrescine has on the O. volvulus and, in comparison, on the Caenorhabditis elegans and human AdoMetDC. Bis(aralkyl)- and bis(alkyl)-substituted polyamine analogues with a 3-7-3 backbone were found to inhibit AdoMetDC activities, however, probably without interfering with the putrescine stimulation. The best inhibitor, BW-1, was about 10-fold more effective against O. volvulus AdoMetDC than against the human enzyme. Unexpectedly, BW-1 was determined to be a competitive inhibitor with respect to AdoMet, having a Ki value of 310 uM for the putrescine-stimulated human AdoMetDC. Furthermore, we show for the O. volvulus and the human enzyme that the degree of inhibition by BW-1 depends on the actual putrescine concentration.
Clinical Relevance of Matrix Metalloproteinase-13 Determined with a New Highly Specific and Sensitive ELISA in Ascitic Fluid of Advanced Ovarian Carcinoma Patients
Authors: Hantke B. , Harbeck N. , Schmalfeldt B. , Claes I. , Hiller O. , Luther M.-O. , Welk A. , Kuhn W. , Schmitt M. , Tschesche H. , Muehlenweg B.
Published: September 2004

Matrix metalloproteinases (MMPs) are involved in many physiological and pathophysiological processes, including tumor cell invasion and metastasis. For one member of this family, MMP-13 (collagenase-3), a new, highly specific ELISA with a sensitivity of 0.5 ng MMP-13/ml was established. The protein levels of MMP-13 in ascitic fluids of 30 patients with advanced ovarian cancer FIGO stage III (n=19) and IV (n=11) were measured with this ELISA. Using a cutoff value of 0.5 ng MMP-13/mg total protein, two patient subpopulations with short (median 16 months) and long (median 36 months) overall survival were identified. Together with other prognostic markers, determination of MMP-13 in ascitic fluid may help to identify patients at risk for early death and help to individualize adjuvant therapy.
Anti-Mouse GPI-PLD Antisera Highlight Structural Differences between Murine and Bovine GPI-PLDs
Authors: Gregory P. , Ziemiecki A. , Zürcher G. , Brodbeck U. , Bütikofer P.
Published: September 2004

Despite its well characterised biochemistry, the physiological role of glycosylphosphatidylinositolspecific phospholipase D (GPIPLD) is unknown. Most of the previous studies investigating the distribution of GPI-PLD have focused on the human and bovine forms of the enzyme. Studies on mouse GPI-PLD are rare, partly due to the lack of a specific antimouse GPI-PLD antibody, but also due to the apparent low reactivity of existing antibodies to rodent GPI-PLDs. Here we describe the isolation of a mouse liver cDNA, the construction and expression of a recombinant enzyme and the generation of an affinitypurified rabbit antimouse GPI-PLD antiserum. The antibody shows good reactivity to partially purified murine and purified bovine GPI-PLD. In contrast, a rat antibovine GPI-PLD antibody shows no reactivity with the mouse enzyme and the two antibodies recognise different proteolytic fragments of the bovine enzyme. Comparison between the rodent, bovine and human enzymes indicates that small changes in the amino acid sequence of a short peptide in the mouse and bovine GPI-PLDs may contribute to the different reactivities of the two antisera. We discuss the implications of these results and stress the importance of antibody selection while investigating GPI-PLD in the mouse.
Optimization of a Violin Top with a Combined Laminate Theory and Honeycomb Model of Wood
Authors: Carlsson P. , Tinnsten M.
Published: September 2004

Stochastic optimization with the simulated annealing method (SA) is performed on a violin top
made of Norway spruce (Picea Abies). A numerical example is presented which shows that it is
possible, through changes in thickness variables, to compensate for changes in vibration properties
caused by a variation in the material parameters in the top. A material model is also presented for
the blank which considers the influence of density variations in the annual rings, the cellular structure
of wood and reinforcement from the wood rays.
Oxidized Derivatives of Lipophilic Extractives Formed during Hardwood Kraft Pulp Bleaching
Authors: Freire C. S. R. , Silvestre A. J. D. , Neto C. Pascoal
Published: September 2004

The structural changes of E. globulus wood extractives during bleaching with chlorine dioxide (D),
oxygen (O), ozone (Z) and hydrogen peroxide (P) were studied. The detailed characterisation of
the extractive derivatives detected in the partially bleached D, O, P and Z pulps was achieved by
performing reactions of pure reference compounds with the different bleaching agents. The results
show that the unsaturated sterols and fatty acids are extensively degraded during chlorine dioxide
and ozone bleaching and only partially degraded during oxygen and hydrogen peroxide bleaching.
The corresponding saturated extractives as well as the long chain aliphatic alcohols and ω-hydroxyfatty
acids were stable during bleaching. The main oxidation products of β-sitosterol and oleic
and linoleic acids, including one chlorinated derivative of linoleic acid, were identified here for the
first time in E. globulus bleached pulps and bleaching filtrates.
Entwurf einer flachheitsbasierten Vorsteuerung für die induktive Erwärmung beim Thixoforming (Flatness Based Control of the Inductive Heating for Thixoforming)
Authors: Fleck Christian , Schönbohm Alexander
Published: September 2004

Thixoforming ist ein neuartiges Formgebungsverfahren, das es im Vergleich zu klassischen Formgebungsverfahren ermöglicht, Bauteile mit höheren Festigkeitswerten und komplexeren Bauformen zu fertigen. Dazu wird die Werkstofflegierung in einem teilflüssigen Zustand verarbeitet, d. h. das Werkstück wird so erwärmt, dass es sich innerhalb des Liquidus-Solidus-Intervalls seiner Legierung befindet und der Werkstoff teilweise aufschmilzt. Die Erwärmung muss möglichst schnell erfolgen, ohne dabei die Randbereiche des Werkstücks zu überhitzen. Da im industriellen Einsatz, in Ermangelung einer geeigneten Temperaturmesstechnik, gesteuerte Anlagen überwiegen, wird in diesem Beitrag eine Methode vorgestellt, die auf der Theorie der Flachheit von Systemen mit verteilten Parametern basiert und mit der geeignete Steuertrajektorien für die induktive Erwärmung von Aluminiumbolzen berechnet werden können. Dazu wird zunächst die das System beschreibende partielle Differentialgleichung vorgestellt und davon ausgehend ein flacher Ausgang des Systems im Zeitbereich bestimmt. Mithilfe des flachen Ausgangs wird eine geeignete Steuertrajektorie für die Stellgröße des Systems berechnet, mittels derer die Temperatur der Billetmitte einem gegebenen Zeitverlauf folgt. Anhand von numerischen Simulationen wird der Erfolg der vorgestellten Methode diskutiert.
Flachheitsbasierte Steuerung und Regelung eines Wärmeleitungssystems (Flatness-based Feedforward and Feedback Control of a Heat Conduction System)
Authors: Meurer Thomas , Zeitz Michael
Published: September 2004

Das lineare Modell eines örtlich eindimensionalen Wärmeleiters wird als Beispiel verwendet, um die flachheitsbasierte Steuerung und Regelung von parabolischen Systemen mit verteilten Parametern zu erläutern. Das betrachtete Wärmeleitermodell mit Randeingriff erlaubt den flachheitsbasierten Entwurf einer Steuerung mithilfe des inversen Systems, um eine hinreichend glatte Trajektorie des Ausgangs zu realisieren. Ein neues Verfahren zum Regler- und Beobachterentwurf ermöglicht die durchgängige flachheitsbasierte Synthese einer Folgeregelung mit Vorsteuerung und Zustandsschätzung. Dies wird beispielhaft für die Steuerung und Regelung des Übergangs zwischen stationären Temperaturprofilen gezeigt und anhand von Simulationsergebnissen diskutiert.
Eine neue Methode zur Regelung von Strecken mit Stellbegrenzung (A New Method for the Control of Systems with Input Saturation)
Authors: Hippe Peter
Published: September 2004

In einem gut gedämpft ausgelegten linearen Regelkreis kann sich eine Stellbegrenzung destabilisierend auswirken. Dieses Phänomen wird üblicherweise als Windup bezeichnet. Fast alle bisher bekannten Windup-Vermeidungsmaßnahmen treten erst dann in Aktion, wenn das Stellsignal den Begrenzungswert das erste Mal überschreitet. Obwohl dies bei stabilen Regelstrecken unproblematisch ist, hat es bei instabilen Systemen unter Umständen zur Konsequenz, dass sich mit solchen Maßnahmen eine Destabilisierung des Regelkreises nicht verhindern lässt. In diesem Beitrag wird nun ein neues Verfahren zur Vermeidung von Windup vorgestellt, das auf einer Trennung zwischen Führungsgrößen-Aufschaltung und Störausregelung beruht. Dadurch gelingt es, einen Teil des begrenzten Stellsignal-Bereiches für die Störbeseitigung und den verbleibenden Teil für das Führungsverhalten zu reservieren. Dies erlaubt die Auslegung von Regelungen mit gesicherter Stabilität bei exponentiell instabilen Regelstrecken mit Stellsignalbegrenzung und es ist gleichermaßen auch bei stabilen Strecken einsetzbar. Anhand der Regelung eines instabilen Systems wird die Anwendung des neuen Verfahrens demonstriert.
Geometrischer Zugang zur Polzuweisbarkeit mittels konstanter Ausgangsrückführungen (Geometric Approach to Pole Assignability by Means of Static Output Feedback)
Authors: Reinschke Kurt J. , Fritsche Oliver
Published: September 2004

Dieser Beitrag behandelt die beliebige Polzuweisbarkeit mithilfe statischer Ausgangsrückführungen bei linearen zeitinvarianten MIMO-Übertragungssystemen. Durch Nutzung von Ergebnissen aus der algebraischen Geometrie können Bedingungen für beliebige Polzuweisbarkeit abgeleitet werden. Alle zulässigen statischen Rückführungen lassen sich als Punkte in einer Grassmannschen Mannigfaltigkeit in einem projektiven Raum deuten. Unter der Annahme, dass das Produkt der Anzahl der skalaren Ein- und Ausgänge größer als die dynamische Ordnung des Systems ist, werden eine notwendige und eine hinreichende Bedingung für die beliebige Polzuweisbarkeit formuliert und bewiesen. Die Verfasser stellen ein Verfahren zur numerischen Ermittlung einer konstanten Ausgangsrückführmatrix vor, die die gewünschte Polplatzierung bewirkt. Anhand eines nicht-trivialen Beispiels werden die Rechenschritte des Verfahrens im Detail illustriert.
H
∞-Regelung von zeitdiskreten Deskriptorsystemen (H
∞ Control of Discrete-Time Descriptor Systems)
Authors: Rehm Ansgar , Allgöwer Frank
Published: September 2004

Die vorliegende Arbeit stellt einen theoretischen Beitrag zur H
∞-Regelung von zeitdiskreten Deskriptorsystemen dar. Es wird das Problem betrachtet, ein gesteuertes zeitdiskretes Deskriptorsystem durch statische Rückführung des Deskriptorvektors zu stabilisieren und gleichzeitig sicherzustellen, dass der geschlossene Regelkreis kausal ist und einer vorgegebenen H
∞-Normbeschränkung genügt. Der vorgestellte Zugang zu diesem Problem basiert auf einer Charakterisierung von stabilen, kausalen und H
∞-normbeschränkten Deskriptorsystemen mithilfe von linearen Matrixungleichungen (LMIs). Die zugeordnete Matrixvariable ist eng mit der Ljapunowfunktion des gegebenen Deskriptorsystems verknüpft. Angewandt auf den Fall des Regelungsproblems liefert dieses Resultat nichtlineare Matrixungleichungen, die zusätzlich zur Ljapunowmatrix noch die Rückführmatrix als unbekannte Matrixvariable enthalten. In dieser Arbeit wird ein Verfahren entwickelt, das es erlaubt, diese nichtlinearen Matrixungleichungen auf LMIs zurückzuführen, und sie damit einer effektiven numerischen Behandlung zugänglich macht.
Formale Methoden für implizite dynamische Systeme (A Formal Approach for Implicit Dynamic Systems)
Authors: Schlacher Kurt , Zehetleitner Kurt
Published: September 2004

Die Modellierung komplexer dynamischer Systeme führt oft auf Sätze von algebraischen Gleichungen und gewöhnlichen Differentialgleichungen. Dieser Beitrag präsentiert nun Methoden für implizite Systeme basierend auf der formalen Theorie von gewöhnlichen Differentialgleichungen. Es wird gezeigt, dass gewisse implizite Systeme, man nennt sie formal integrable, Eigenschaften aufweisen, die viele Untersuchungen ohne Überführung in eine explizite Form gestatten. Dabei wird ein dynamisches System als eine Untermannigfaltigkeit mit einer speziellen geometrischen Struktur aufgefasst. Die Form der Gleichungen entspricht dann lediglich einer speziellen Parametrierung dieser Untermannigfaltigkeit. Da man unter gewissen Regularitätsannahmen jedes implizite System in ein formal integrables überführen kann, stellt diese Klasse ein natürliches Bindeglied zwischen den expliziten und den impliziten Systemen dar. Auf Basis dieser Betrachtung werden zuerst Ergebnisse für den allgemeinen Fall präsentiert, dann werden Systeme, die linear in den Ableitungen sind, ausführlicher untersucht. Zum Abschluss wird die Theorie auf den linearen und zeitinvarianten Fall angewandt.
Amplitudes of Composition Fluctuations in the Simplest Chemical Reaction Equilibrium
Authors: Šolc M. , Hostomský J.
Published: September 2004

We present a numerical study of equilibrium composition fluctuations in a system where the reaction X1 ⇔ X2 having the equilibrium constant equal to 1 takes place. The total number of reacting particles is N. On a discrete time scale, the amplitude of a fluctuation having the lifetime 2r reaction events is defined as the difference between the number of particles X1 in the microstate most distant from the microstate N/2 visited at least once during the fluctuation lifetime, and the equilibrium number of particles X1, N/2. On the discrete time scale, the mean value of this amplitude, m̅(r̅), is calculated in the random walk approximation. On a continuous time scale, the average amplitude of fluctuations chosen randomly and regardless of their lifetime from an ensemble of fluctuations occurring within the time interval (0,z), z → ∞, tends with increasing N to ~1.243 N
0.25. Introducing a fraction of fluctuation lifetime during which the composition of the system spends below the mean amplitude m̅(r̅), we obtain a value of the mean amplitude of equilibrium fluctuations on the continuous time scale equal to ~1.19√N. The results suggest that using the random walk value m̅(r̅) and taking into account a) the exponential density of fluctuations lifetimes and b) the fact that the time sequence of reaction events represents the Poisson process, we obtain values of fluctuations amplitudes which differ only slightly from those derived for the Ehrenfest model.
Size Illusions as a Phenomenon of Limited Information Processing Capacity
Authors: Kreiner W. A.
Published: September 2004

The results of a study on the moon illusion are reported, in which the relationship between the illusion, vision and the distance of the horizon have been investigated. The illusion is explained on the basis of a model derived from information theory. Due to the limited channel capacity of the visual system, the size and the resolution of an image are related to each other in such a way, that resolution can only be increased when the size is simultanously reduced. As a result of this constraint, the conspicuity area has to be reduced in order to resolve more detail. Assuming that the visual image is projected onto what is effectively an internal visual memory screen, the size illusion can be explained. A mathematical expression is derived which is fitted to the results of various experiments performed by several other authors in order to measure size constancy. Based on this model two versions of the moon illusion are discussed, as well as their relationship to atmospheric effects and to perspective. The horizon-distance hypothesis is regarded as a special case within this more general model.
Isopiestic Investigation of the Systems FeCl2–(Na, K, Mg, Ca)Cl
n
–H2O at 298.15 K
Authors: Moog Helge C. , Hagemann Sven , Rumyantsev Alexey V.
Published: September 2004

Isopiestic measurements were performed in aqueous FeCl2-solutions and in ternary systems of the type FeCl2–MCl
n
–H2O (M = Na, K, Mg, Ca). Numeric data for water-isoactivity lines are presented and pertinent osmotic coefficients are calculated. The obtained data were recalculated using Pitzer’s equations. Pertinent parameters are given.
Isopiestic Investigation of the Systems Fe2(SO4)3–H2SO4–H2O, FeCl3–H2O, and Fe(III)–(Na, K, Mg, Ca)Cl
n
–H2O at 298.15 K
Authors: Rumyantsev Alexey V. , Hagemann Sven , Moog Helge C.
Published: September 2004

Isopiestic measurements were performed in binary and ternary systems of the type Fe2(SO4)3–H2SO4–H2O, FeCl3–H2O, and FeCl3–MCl
n
–H2O (M = Na, K, Mg, or Ca). Numeric data for water isoactivity lines are presented and osmotic coefficients are calculated. The obtained data were recalculated using Pitzer’s equations. Pertinent parameters are given.
Conductometric Study of Some Tetraalkylammonium Bromides in 2-Ethoxyethanol in the Temperature Range 35–50 °C
Authors: Haldar Purushottam , Das Bijan
Published: September 2004

The electrical conductances of the solutions of four tetraalkylammonium bromide salts (R4NBr), namely tetraethylammonium bromide (Et4NBr), tetrapropylammonium bromide (Pr4NBr), tetrapentylammonium bromide (Pen4NBr) and tetraheptylammonium bromide (Hep4NBr) in 2-ethoxyethanol have been reported at 35, 40, 45 and 50 °C. The conductance data have been analyzed by the 1978 Fuoss conductance–concentration equation in terms of the limiting molar conductance (Λ0), the association constant (K
A) and the association diameter (R). The ionic contributions to the limiting molar conductance have also been estimated. Appreciable ionic association was observed for all of these electrolytes in 2-ethoxyethanol. The tetraalkylammonium ions (R4N+) were found to remain scarcely solvated in the present solvent medium within the temperature range investigated here. The solvation of the bromide ion in these tetraalkylammonium bromide is found to be weakened as soon as the ion-pairs are formed. An increase in the temperature results in a lower level of ion-pairing for each of these salts.
Delivery Device Patents on GLP-1 Receptor Agonists
Authors: Alhiary Rasha , Gabriele Sarah , Kesselheim Aaron S. , Tu S. Sean , Feldman William B.
Published: February 2024

This study analyzed the US Food and Drug Administration–listed patents on glucagon-like peptide 1 (GLP-1) receptor agonists to determine their claim characteristics and the potential barriers they pose to generic entry.
Possible Digoxin-Related Toxic Effects in a Patient
Authors: Lee Chan-Hee , Scheinman Melvin M.
Published: February 2024

This case report describes a patient in their 70s with hypertension and heart failure presenting to the emergency department with chest discomfort, nausea, anorexia, and weakness.
Trends in Current Electronic Cigarette Use Among Youths by Age, Sex, and Race and Ethnicity
Authors: Mattingly Delvon T. , Hart Joy L.
Published: February 2024

This cross-sectional study examines prevalence of electronic cigarette use among youths by age, sex, and race and ethnicity from 2013 to 2022.
Food Insecurity Is a Source of Toxic Stress
Authors: Leung Cindy W. , Odoms-Young Angela , Essel Kofi
Published: February 2024

This Viewpoint discusses food insecurity as a source of toxic stress that can affect children’s health and advocates for developing research, clinical, and policy approaches to address the root causes of food insecurity.
Safety, pharmacokinetics, and pharmacodynamics of nomlabofusp (CTI‐1601) in Friedreich's ataxia
Authors: Clayton Russell , Galas Teresa , Scherer Noreen , Farmer Jennifer , Ruiz Nancy , Hamdani Mohamed , Schecter Devin , Bettoun David
Published: February 2024

Objective

Current treatments for Friedreich's ataxia, a neurodegenerative disorder characterized by decreased intramitochondrial frataxin, do not address low frataxin concentrations. Nomlabofusp (previously CTI‐1601) is a frataxin replacement therapy with a unique mechanism of action that directly addresses this underlying frataxin deficiency. Phase 1 studies assessed the safety, pharmacokinetic, and pharmacodynamic profiles of subcutaneously administered nomlabofusp in adults with Friedreich's ataxia.

Methods

Patients were enrolled in two Phase 1, double‐blind, placebo‐controlled studies. The single ascending‐dose (SAD) study (NCT04176991) evaluated single doses of nomlabofusp (25, 50, 75, or 100 mg) or placebo. The multiple ascending‐dose (MAD) study (NCT04519567) evaluated nomlabofusp (25 mg daily for 4 days then every third day, 50 mg daily for 7 days then every 2 days, or 100 mg daily) or placebo for 13 days.

Results

Patients aged 19–69 years were enrolled (SAD, N = 28; MAD, N = 27). Nomlabofusp was generally well tolerated through 13 days. Most adverse events were mild and resolved quickly. No serious adverse events or deaths were reported. Peak nomlabofusp plasma concentrations occurred 15 min after subcutaneous administration. Nomlabofusp plasma exposures increased with increasing doses and daily administration and decreased with reduced dosing frequency. Increased frataxin concentrations were observed in buccal cells, skin, and platelets with higher and more frequent nomlabofusp administration.

Interpretation

Results from this study support a favorable safety profile for nomlabofusp. Subcutaneous nomlabofusp injections were quickly absorbed; higher doses and daily administration resulted in increased tissue frataxin concentrations. Future studies will evaluate longer‐term safety and possible efficacy of nomlabofusp.
Safety, Tolerability, and Pharmacodynamics of the ADAMTS‐5 Nanobody M6495: Two Phase 1, Single‐Center, Double‐Blind, Randomized, Placebo‐Controlled Studies in Healthy Subjects and Patients With Osteoarthritis
Authors: Bihlet Asger Reinstrup , Balchen Torben , Goteti Kosalaram , Sonne Jesper , Ladel Christoph , Karsdal Morten Asser , Ona Victor , Moreau Flavie , Waterhouse Roseann , Bay‐Jensen Anne‐Christine , Guehring Hans
Published: February 2024

Objective

To assess the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of single and multiple injections of M6495, a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS‐5)  nanobody, in healthy volunteers and patients with osteoarthritis.

Methods

Two randomized, placebo‐controlled, double‐blind studies were performed. Study 1 enrolled 54 healthy male volunteers who received one subcutaneous (s.c.) injection of M6495 (1‐300 mg) or placebo (ratio 2:1), evaluating safety, PK, and PD as changes in the serum aggrecan fragment alanine‐arginine‐glycine‐serine (ARGS). Study 2 enrolled 32 patients with osteoarthritis with Kellgren–Lawrence grades 2 to 4 and pain greater than or equal to 40 on the Western Ontario and McMaster Universities Arthritis Index pain subscale at screening and evaluated the safety, PK, and PD of three doses every two weeks (75‐300 mg per dose) or six once‐weekly M6495 s.c. doses (300 mg) or placebo (ratio 3:1) over 106 days’ follow‐up.

Results

M6495 in single and multiple doses of less than or equal to 300 mg s.c. weekly was well tolerated with no clinically significant changes in any safety parameter. Adverse events more frequently reported in the M6495 groups were mostly mild cases of injection site reactions, myalgia, and nausea, which resolved after treatment cessation. The elimination half‐life of single s.c. doses of M6495 ranged from 79 to 267 hours. M6495 administration substantially reduced serum ARGS levels, indicative of target engagement and indicating disease‐modifying potential of M6495.

Conclusion

Treatment with M6495 in single and multiple doses up to and including 300 mg s.c. was found to be well tolerated and adequately safe for further clinical evaluation of potential disease‐modifying effects.
Dynamic event‐triggered control for the leader‐following consensus of multi‐agent systems with input time delay
Authors: Pu Xingcheng , Hou Jiaang , Li Yonghong
Published: February 2024

In this article, the leader‐following consensus of a kind of linear homogeneous MASs (multi‐agent systems) with input time delay is investigated. To realize leader‐following consensus, a novel distributive input control protocol based on dynamic event‐triggered mechanism is proposed. In this novel protocol, internal dynamic variables are employed to reduce the burden of communication and exclude the Zeno phenomenon. By utilizing the graph algebra, stability analysis and Lyapunov theory, some sufficient conditions have been obtained for the consensus of this MASs. The effectiveness of our approach is illustrated by some simulation examples. Compared with the given achievements, the obtained results have better ability in accelerating convergence rate and reducing the burden of communication.
A Solar and Seawater Co‐Involved Durable Rechargeable Battery Enabled by Crown Ether‐Rich Polymer‐Mediated Photoelectrodes
Authors: Wang Xiaotong , Li Jing , Liu Cong , Lin Yi , Yang Fan , Zhong Linfeng , Zhang Yang , Yu Dingshan
Published: February 2024

The first flow‐type solar and seawater co‐mediated sodium‐air rechargeable battery (SSRB) for efficient solar‐to‐electrochemical energy conversion/storage is established. Such SSRB is enabled by a robust self‐regulated CEP/ZnWO4/WO3 heterojunction photoelectrochemical electrodes (PE) by passivating predesigned crown ether‐rich photoresponsive covalent organic polymer (CEP) layers onto ZnWO4‐modified WO3 nanosheet arrays. The PE design utilizes the previously‐unexplored self‐mediated effect of CEP to endow PE with superior stability, facilitated electrode reaction kinetics, and high efficiency of spatial charge separation simultaneously. This leads to remarkable light‐enhanced oxygen evolution catalysis with impressive photocurrent density up to 6.1 mA cm−2 at 1.23 V versus RHE in seawater – surpassing metal‐oxide‐based PEs ever reported for seawater splitting. Thus, the SSRB breaks the limit of the equilibrium voltage (3.47 V) of conventional seawater sodium‐air cells to deliver a low charge voltage of 2.71 V along with stable photo‐charge over 100 h and good photo‐charge/normal discharge cycling stability over 240 h – superior to almost all existing light‐involved air batteries. Combined experimental and modeling studies for the first time unveil the multi‐regulation effects of CEP passivation which prevents detrimental Cl‐corrosion, and promote oxygen evolution kinetics.
Necklace‐Structured Silicon Suboxide‐Based Anode Materials with Multiple Carbon Networks for Stable Lithium Storage
Authors: Zhang Yuanyuan , Yang Wei , Liu Xue , Ma Ganggang , Hu Guangwu , Liu Zhenhui , Yu Ruohan , Zhuang Dingyue , Xu Jie , Zhao Dongyuan , Mai Liqiang , Zhou Liang
Published: February 2024

Silicon suboxide (SiOx) attracts great attentions from both academy and industry owing to its higher capacity than graphite and smaller volume swelling than Si, making it possible to achieve a tradeoff between capacity and cycling stability. Whereas, the volume expansion problem and poor electrical conductivity of SiOx severely hinder its practical applications. Herein, a unique necklace‐structured SiOx‐based anode material consisting of carbon nanotube wired SiOx/C@C spheres with a surface carbon coating layer (CNT@SiOx/C@C) is constructed. The multiple carbon networks wire the whole composite anode material, effectively confining the volumetric variation of SiOx, and enhancing the structural integrity of the electrode. The as‐synthesized necklace‐structured CNT@SiOx/C@C manifests decent lithium storage behaviors in terms of discharge capacity (857.7 mAh g−1 at 0.1 A g−1), cyclability (81.7% capacity retention over 100 cycles at 0.1 A g−1), and rate capability (333.3 mAh g−1 at 10 A g−1). This study demonstrates the effectiveness of constructing multiple carbon networks for tackling the volume swelling and conductivity issues of SiOx. It is also anticipated that this structural design would be generally applied to other high‐capacity electrode materials suffering from large volume fluctuation and low conductivity.
Multiple Redox‐Active Cyano‐Substituted Organic Compound Integrated with MXene Nanosheets for High‐Performance Flexible Aqueous Zn‐Ion Battery
Authors: Zhao Doudou , Li Zhirui , Xu Da , Yang Zhenglong
Published: February 2024

An eco‐friendly organic compound, with rich redox sites, considered a promising cathode material for aqueous zinc‐ion batteries (AZIBs). Despite its potential, limited specific capacity and cycle instability impede its practical application. Herein, an organic compound, hexaazatriphenylene hexacarbonitrile (6CN‐HAT), is designed with a π–π conjugated aromatic structure, and integrated with MXene nanosheets to construct a flexible self‐supporting electrode (6CN‐HAT@MXene). Ex‐situ characterizations and theoretical calculations verify that the charge storage mechanism predominantly involves coordination and non‐coordination reactions between reactive C═N and ─CN sites with cations. The introduction of MXene nanosheets not only bolster the stability and electronic conductivity of the 6CN‐HAT@MXene but also expose additional active sites for cation coordination. As a cathode material in AZIBs, 6CN‐HAT@MXene exhibits an outstanding discharge specific capacity of 413 mAh g−1 at 0.05 A g−1. Remarkably, even after 5000 cycles at 5 A g−1, the discharge capacity retained 91%. Furthermore, based on the 6CN‐HAT@MXene electrode, a flexible micro‐zinc‐ion batteries with high area capacity of 257.4 mF cm−2 is prepared using laser cutting technology, highlighting its potential for future applications in portable and wearable electronic devices.
Porous Carbon Cloth@CoSe2 as Kinetics‐Enhanced and High‐Loading Integrated Sulfur Host for Lithium–Sulfur Batteries
Authors: Wang Cheng , Liu Ruiqing , Liu Wenxiu , Zhu Wenfeng , Yang Xiaoxuan , Wu Qiang , Xie Kun , Shen Lvgen , Wu Jingyi , Liu Yiran , He Lulu , Chen Zibo , Chen Jianyu , Zhao Cuie , Lin Xiujing , Shi Li , Zhao Jin , Feng Xiaomiao , Wu Gang , Ma Yanwen
Published: February 2024

Carbon cloth (CC) possesses great potential as a sulfur host because of its excellent conductivity, flexibility, and easily modified free‐standing structure. However, the previous works do not take full advantage of CC except for the role of support and current collector. The smooth surface, small specific surface area, and poor binding force between coating materials and CC matrix are unfavorable for loading coating materials. The slow redox kinetics and low sulfur loading of sulfur cathodes still seriously restrict the development of Lithium–Sulfur (Li–S) batteries. Herein, the porous carbon cloth loading cobalt selenide (PCC@CoSe2) is constructed as an integrated sulfur host through a pore‐creating and selenylation strategy. The pore‐creating engineering greatly optimizes the 3D pore structure of CC to raise the sulfur and catalyst loading and provides enough space to accommodate the volume change of sulfur species. In addition, CoSe2 particles as nano‐catalyst units embedded in PCC can effectively adsorb‐catalyze polysulfides and improve the reaction kinetics. The resulting integrated sulfur cathode has realized the high‐efficiency polysulfide catalytic conversion and fast lithium ion migration, significantly enhancing redox kinetics and sulfur loading.
Lignin‐Alkali Metal Ion Self‐Catalytic System Initiated Rapid Polymerization of Hydrogel Electrolyte with High Strength and Anti‐Freezing Ability
Authors: Su Huawei , Guo Qingqing , Qiao Congde , Ji Xingxiang , Gai Ligang , Liu Libin
Published: February 2024

Hydrogel electrolyte is not resistant to freezing and has weak mechanical properties, and its fabrication is time‐consuming and energy‐consuming, limiting its application. Here, a simple, universal, and fast gelation based on dealkaline lignin (DL) ‐alkali metal ions is developed. The complex formed by catechol and alkali metal ions promotes the equilibrium of redox reactions. The produced SO4−·, OH· and singlet oxygen (1O2) radicals are responsible for the rapid polymerization of vinyl monomers. Alkali metal ions play a dual role in the rapid polymerization and frost resistance of hydrogel electrolytes. By modulating the mass ratio of DL and metal ion concentration, the preferred hydrogel electrolyte can be fabricated in an alkaline aqueous solution for 4 min at room temperature and possesses excellent anti‐freezing performance (0.51 mS cm−1 at −40 °C) and strong mechanical properties (tensile stress: 0.4 MPa, strain: 1125%). The hydrogel electrolyte‐assembled supercapacitor exhibits high stability at low temperatures. The specific capacitance retention is 89.7 % and 88.7 % after 5000 charge/discharge cycles at 25 and −20 °C, respectively. The lignin‐alkali metal ions self‐catalytic system completely different from the reported lignin‐oxidizing metal ion system will open up a new way for the fabrication of anti‐freezing ionic conductors and energy storage devices.
18.62%‐Efficiency Binary Organic Solar Cells with a PEDOT1:PSS2.80 Buffer Layer
Authors: Zeng Jixi , Fan Xi , Wang Jinzhao , Li Jia , Chen Jiwen , Hui Kwun Nam , Ai Ling , Fang Junfeng , Song Weijie
Published: February 2024

Binary organic solar cells (OSCs) having a controllable phase‐separated morphology of active layers and simple solution manufacturing are desirable for organic photovoltaic adaptation. However, low hole mobility and an unbalanced hole‐ and electron transport reduce the power conversion efficiency (PCE) of the OSCs. Here, a highly efficient binary OSC with a poly(3,4‐ethylenedioxythiophene):poly(4‐styrenesulfonate) (PEDOT:PSS) buffer layer as a hole transport layer (HTL) via using a water‐soluble sulfonate to wrap the PEDOT:PSS core‐shell structures in solutions is reported. The PEDOT1:PSS2.80 buffer layers have good merits including i) a smooth, homogeneous, and hydrophilic surface for an intimate contact, ii) a high work function and raised surface potentials with much uniform distributions for an energy band alignment, and iii) a high optical transmittance in the broad spectral region from 400 to 1100 nm along with an improved electrical conductivity. Benefiting from a raised hole mobility and a better charge‐mobility balance, the solution‐processed binary OSCs yielded a high PCE of 18.62%. 18.62% is one of the highest values among these binary OSCs based on the PEDOT:PSS HTLs and PM6:L8‐BO active layers. The PEDOT1:PSS2.80 buffer layers are superior to the pristine PEDOT1:PSS2.60 buffer layers in terms of raising the OSC efficiency.
Improved Performance of Lead‐Free Perovskite Solar Cells Based on Multi‐Absorber MASnI3/CsGeI3 Heterojunction by Device Simulation
Authors: Huang Xiaokun , Yang Aijun , Li Jiansheng , Jiang Linqin , Lin Lingyan , Qiu Yu
Published: February 2024

Lead‐free perovskite solar cell (PSC) is the direction of future development of PSCs due to its reduced toxicity. However, the power conversion efficiency (PCE) of the lead‐free PSCs is still lagging behind their lead‐based counterparts, which hinders their further application. Multi‐absorber approach can effectively overcome this problem as it allows the maximum utilization of solar spectrum. Therefore, in this study a novel lead‐free MASnI3/CsGeI3 heterojunction structure is proposed to boost the performance of PSCs based on single CsGeI3 absorption layer. The critical device parameters including absorber thickness, defect density, doping concentration, and back contact work function are studied and optimized using the numerical software SCAPS‐1D. Under optimized conditions, PSCs based on Sn/Ge bilayer structure yield a considerable PCE of 16.15%, significantly higher than the single CsGeI3 based PSCs (optimized PCE of 7.43%) with higher thermal stability. The simulation results indicate a huge potential of the proposed multi‐absorber heterojunction structure for highly efficient lead‐free PSCs, which will contribute to achieving clean and sustainable energy in the future.
Mechanical Stretch α‐Cyclodextrin Pseudopolyrotaxane Elastomer with Reversible Phosphorescence Behavior
Authors: Zhang Yi , Chen Yong , Li Jian‐Qiu , Liu Song‐En , Liu Yu
Published: February 2024

Polyethylene glycol chains in two terminals of the naphthalene functional group are threaded into α‐cyclodextrin cavities to form the pseudopolyrotaxane (NPR), which not only effectively induces the phosphorescence of the naphthalene functional group by the cyclodextrin macrocycle confinement, but also provides interfacial hydrogen bonding assembly function between polyhydroxy groups of cyclodextrin and waterborne polyurethane (WPU) chains to construct elastomers. The introduction of NPR endows the elastomer with enhanced mechanical properties and excellent room temperature phosphorescent (RTP) emission (phosphorescence remains in water, acid, alkali, and organic solvents, even at 160 °C high temperatures). Especially, the reversible mechanically responsive room temperature phosphorescence behavior (phosphorescence intensity increased three times under 200% strain) can be observed in the mechanical stretch and recover process, owing to strain‐induced microstructural changes further inhibiting the non‐radiative transition and the vibration of NPR. Therefore, changing the phosphorescence behavior of supramolecular elastomers through mechanical stretching provides a new approach for supramolecular luminescent materials.
Axially Chiral Organic Semiconductors for Visible‐Blind UV‐Selective Circularly Polarized Light Detection
Authors: Kwon Yejin , Jung Je‐Yeon , Lee Won Bo , Oh Joon Hak
Published: February 2024

Technologies that detect circularly polarized light (CPL), particularly in the UV region, have significant potential for various applications, including bioimaging and optical communication. However, a major challenge in directly sensing CPL arises from the conflicting requirements of planar structures for efficient charge transport and distorted structures for effective interaction with CPL. Here, a novel design of an axially chiral n‐type organic semiconductor is presented to surmount the challenge, in which a binaphthyl group results in a high dissymmetry factor at the molecular level, while maintaining excellent electron‐transporting characteristics through the naphthalene diimide group. Experimental and computational methods reveal different stacking behaviors in homochiral and heterochiral assemblies, yielding different structures: Nanowires and nanoparticles, respectively. Especially, the homochiral assemblies exhibit effective π–π stacking between naphthalene diimides despite axial chirality. Thus, phototransistors fabricated using enantiomers exhibit a high maximum electron mobility of 0.22 cm2 V−1 s−1 and a detectivity of 3.9 × 1012 Jones, alongside the CPL distinguishing ability with a dissymmetry factor of responsivity of 0.05. Furthermore, the material possesses a wide bandgap, contributing to its excellent visible‐blind UV‐selective detection. These findings highlight the new strategy for compact CPL detectors, coupled with the demonstration of less‐explored n‐type and UV region phototransistors.
Identification of Potent siRNA Delivery Peptides Using Computer Modeling
Authors: Men Ke , Liu Mohan , Zhang Xueyan , Yang Yuling , Zhang Rui , Wang Yusi , Hu Die , Zhou Bailing , Yang Li
Published: February 2024

Peptides with suitable aggregation behavior and electrical properties are potential siRNA delivery vectors. However, identifying suitable peptides with ideal delivery and safety features is difficult owing to the variations in amino acid sequences. Here, a holistic program based on computer modeling and single‐cell RNA sequencing (scRNA‐seq) is used to identify ideal siRNA delivery peptides. Stage one of this program consists of a sequential screening process for candidates with ideal assembly and delivery ability; stage two is a cell subtype‐level analysis program that screens for high in vivo tissue safety. The leading candidate peptide selected from a library containing 12 amino acids showed strong lung‐targeted siRNA delivery capacity after hydrophobic modification. Systemic administration of these compounds caused the least damage to liver and lung tissues and has little impact on macrophage and neutrophil numbers. By loading STAT3 siRNA, strong anticancer effects are achieved in multiple models, including patient‐derived xenografts (PDX). This screening procedure may facilitate the development of peptide‐based RNA interference (RNAi) therapeutics.
Revealing Pathway Complexity and Helical Inversion in Supramolecular Assemblies Through Solvent‐Induced Radical Disparities
Authors: Ma Haotian , Cheng Xiaoxiao , Zhang Gong , Miao Tengfei , He Zixiang , Zhang Wei
Published: February 2024

New insights are raised to interpret pathway complexity in the supramolecular assembly of chiral triarylamine tris‐amide (TATA) monomer. In cosolvent systems, the monomer undergoes entirely different assembly processes depending on the chemical feature of the two solvents. Specifically, 1,2‐dichloroethane (DCE) and methylcyclohexane (MCH) cosolvent trigger the cooperative growth of monomers with M helical arrangement, and hierarchical thin nanobelts are further formed. But in DCE and hexane (HE) combination, a different pathway occurs where monomers go through isodesmic growth to generate twisted nanofibers with P helical arrangement. Moreover, the two distinct assemblies exhibit opposite excited‐state chirality. The driving force for both assemblies is the formation of intermolecular hydrogen bonds between amide moieties. However, the mechanistic investigation indicates that radical and neutral triarylamine species go through distinct assembly phases by changing solvent structures. The neutralization of radicals in MCH plays a critical role in pathway complexity, which significantly impacts the overall supramolecular assembly process, giving rise to inversed supramolecular helicity and distinct morphologies. This differentiation in pathways affected by radicals provides a new approach to manipulate chiral supramolecular assembly process by facile solvent–solute interactions.
Incorporating Two Crown Ether Struts into the Backbone of Robust Zirconium‐Based Metal–Organic Frameworks as Custom‐Designed Efficient Collectors for Radioactive Metal Ions
Authors: Li Lei , Kang Kang , Chee Tien‐Shee , Tian Zhenjiang , Sun Qi , Xiao Chengliang
Published: February 2024

The incorporation of crown ether into metal‐organic frameworks (MOFs) is garnered significant attention because these macrocyclic units can fine‐tune the inherent properties of the frameworks. However, the synthesis of flexible crown ethers with precise structures as the fundamental building blocks of crystalline MOFs remains a challenging endeavor, with only a limited number of transition metal examples existing to date. Herein, 18‐crown‐6 and 24‐crown‐8 struts are successfully incorporated into the skeleton of zirconium‐based MOFs to obtain two new and stable crown ether‐based MOFs, denoted as ZJU‐X100 and ZJU‐X102. These newly developed MOFs displayed high porosity and remarkable stability when exposed to various solvents, boiling water, pH values, and even concentrated HCl conditions. Thanks to their highly ordered porous structure and high‐density embedding of specific binding sites within tubular channels, these two MOFs exhibited extremely fast sorption kinetics and demonstrated outstanding performance in the uptake of strontium and cesium ions, respectively. Furthermore, the structures of Sr‐adsorbed ZJU‐X100 and Cs‐adsorbed ZJU‐X102 are solved and confirmed the precise location of Sr2+/Cs+ in the cavity of 18‐crown‐6/24‐crown‐8. This makes modular mosaic of different crown ethers into the skeleton of stable zirconium‐based MOFs possible and promote such materials have broad applications in sorption, sensing, and catalysis.