bluuebunny/crossref_metadata_2025 huggingface dataset:
Schwann Cell Myelination Requires Timely and Precise Targeting of P0 Protein
Authors: Yin X. , Kidd G.J. , Wrabetz L. , Feltri M.L. , Messing A. , Trapp B.D.
Published: July 2002

This report investigated mechanisms responsible for failed Schwann cell myelination in mice that overexpress P0 (P0tg), the major structural protein of PNS myelin. Quantitative ultrastructural immunocytochemistry established that P0 protein was mistargeted to abaxonal, periaxonal, and mesaxon membranes in P0tg Schwann cells with arrested myelination. The extracellular leaflets of P0-containing mesaxon membranes were closely apposed with periodicities of compact myelin. The myelin-associated glycoprotein was appropriately sorted in the Golgi apparatus and targeted to periaxonal membranes. In adult mice, occasional Schwann cells myelinated axons possibly with the aid of endocytic removal of mistargeted P0. These results indicate that P0 gene multiplication causes P0 mistargeting to mesaxon membranes, and through obligate P0 homophilic adhesion, renders these dynamic membranes inert and halts myelination.
Tumor Necrosis Factor Induces Hyperphosphorylation of Kinesin Light Chain and Inhibits Kinesin-Mediated Transport of Mitochondria
Authors: De Vos Kurt , Severin Fedor , Van Herreweghe Franky , Vancompernolle Katia , Goossens Vera , Hyman Anthony , Grooten Johan
Published: July 2002

The molecular motor kinesin is an ATPase that mediates plus end-directed transport of organelles along microtubules. Although the biochemical properties of kinesin are extensively studied, conclusive data on regulation of kinesin-mediated transport are largely lacking. Previously, we showed that the proinflammatory cytokine tumor necrosis factor induces perinuclear clustering of mitochondria. Here, we show that tumor necrosis factor impairs kinesin motor activity and hyperphosphorylates kinesin light chain through activation of two putative kinesin light chain kinases. Inactivation of kinesin, hyperphosphorylation of kinesin light chain, and perinuclear clustering of mitochondria exhibit the same p38 mitogen-activated kinase dependence, indicating their functional relationship. These data provide evidence for direct regulation of kinesin-mediated organelle transport by extracellular stimuli via cytokine receptor signaling pathways.
C–C Chemokines Released by Lipopolysaccharide (LPS)-stimulated Human Macrophages Suppress HIV-1 Infection in Both Macrophages and T Cells
Authors: Verani Alessia , Scarlatti Gabriella , Comar Manola , Tresoldi Eleonora , Polo Simona , Giacca Mauro , Lusso Paolo , Siccardi Antonio G. , Vercelli Donata
Published: July 2002

Human immunodeficiency virus-1 (HIV-1) expression in monocyte-derived macrophages (MDM) infected in vitro is known to be inhibited by lipopolysaccharide (LPS). However, the mechanisms are incompletely understood. We show here that HIV-1 suppression is mediated by soluble factors released by MDM stimulated with physiologically significant concentrations of LPS. LPS-conditioned supernatants from MDM inhibited HIV-1 replication in both MDM and T cells. Depletion of C–C chemokines (RANTES, MIP-1α, and MIP-1β) neutralized the ability of LPS-conditioned supernatants to inhibit HIV-1 replication in MDM. A combination of recombinant C–C chemokines blocked HIV-1 infection as effectively as LPS. Here, we report an inhibitory effect of C–C chemokines on HIV replication in primary macrophages. Our results raise the possibility that monocytes may play a dual role in HIV infection: while representing a reservoir for the virus, they may contribute to the containment of the infection by releasing factors that suppress HIV replication not only in monocytes but also in T lymphocytes.
CD40 Activation Induces Apoptosis in Cultured Human Hepatocytes via Induction of Cell Surface Fas Ligand Expression and Amplifies Fas-mediated Hepatocyte Death during Allograft Rejection
Authors: Afford Simon C. , Randhawa Satinder , Eliopoulos Aristides G. , Hubscher Stefan G. , Young Lawrence S. , Adams David H.
Published: July 2002

We propose that a novel mechanism of hepatocyte apoptosis, involving a cooperative interaction between CD40 and Fas, is involved in the hepatocyte loss of chronic liver allograft rejection. We detected increased hepatocyte expression of Fas, Fas ligand (FasL), and CD40 associated with dropout of centrilobular (acinar zone 3) hepatocytes in chronic allograft rejection. Expression of CD40 ligand (CD40L) was also increased but was largely restricted to CD68+ macrophages. A functional role for CD40 and Fas in hepatocyte apoptosis was demonstrated in vitro using primary human hepatocytes and the HepG2 cell line in both of which apoptosis was induced, not only by cross-linking Fas directly but also via CD40 activation. Our data suggest that CD40 activation induces apoptosis via Fas because (a) ligation of CD40 upregulated hepatocyte FasL expression, and (b) apoptosis induced via activation of CD40 was prevented by a neutralizing monoclonal antibody to FasL. Thus, CD40 engagement triggers apoptosis of human hepatocytes and might amplify Fas-dependent hepatocyte apoptosis in chronic rejection and other inflammatory liver diseases in which Fas-mediated apoptosis is involved.
High Level Expression of Cd43 Inhibits T Cell Receptor/CD3-Mediated Apoptosis
Authors: He You-Wen , Bevan Michael J.
Published: July 2002

In a screen designed to identify genes that regulate T cell receptor (TCR)/CD3-mediated apoptosis, we found that high level expression of CD43 protected T cell hybridomas from activation-induced cell death. The protection appears to result from its capacity to block Fas-mediated death signals rather than from inhibition of the upregulation of Fas and/or Fas ligand after T cell stimulation. We found that peripheral CD4+ T cells can be divided into two subsets based on the level of CD43 surface expression. The CD4+CD43low subset exhibits a naive T cell phenotype, being CD62LhighCD45RBhighCD44low, whereas CD4+CD43high cells exhibit a memory phenotype, being CD62LlowCD45RBlowCD44high. Recent studies have demonstrated that engagement of TCR and Fas induces naive CD4+ T cells to undergo apoptosis, and the same treatment enhances the proliferation of memory CD4+ T cells. We confirm here that peripheral CD4+CD43high T cells are resistant to TCR/CD3-mediated cell death. These results suggest that the expression levels of CD43 on naive and memory CD4+ T cells determine their susceptibility to Fas-dependent cell death and that high level expression of CD43 may be used as a marker to define CD4+ memory T cells. Expression of CD43 provides a novel mechanism by which tumor cells expressing abnormally high levels of CD43 may escape Fas-mediated killing.
Extensions of homeomorphisms between limbs of the Mandelbrot set
Authors: Branner Bodil , Fagella Núria
Published: July 2002

Using holomorphic surgery techniques, we construct a homeomorphism between a neighborhood of any limb without root point of the Mandelbrot set and a neighborhood of any other of equal denominator, in such a way that the limbs are mapped to each other. On the limbs, the homeomorphism coincides with that constructed in “Homeomorphisms between limbs of the Mandelbrot set” (J. Geom. Anal. 9 (1999), 327–390) which proves – without assuming local connectivity of the Mandelbrot set – that these maps are compatible with the embedding of the limbs in the plane. Outside the limbs, the constructed extension is quasi-conformal.
WEBMAP: radiation hybrid mapping on the WWW.
Authors: Newell W , Sanseau P , Riley J , Lyall A
Published: July 2002

SUMMARY: A Java interface to radiation hybrid (RH) mapping software is described which enables users to build and interactively refine RH maps over the web. AVAILABILITY: The Java applets described here are available on the internet at http://www.oxmol.com/biolib/webmap/.
BBID: the biological biochemical image database
Authors: Becker Kevin G. , White Shawnte L. , Muller Jerri , Engel James
Published: July 2002

Summary: The Biological Biochemical Image Database is a WWW accessible relational database of archived images from research articles that describe regulatory pathways of higher eukaryotes. Pathway information is annotated and can be queried in the study of complex gene expression. In this way, complex regulatory pathways can be tested empirically in an efficient manner in the context of large-scale gene-expression systems.

Availability: http://bbid.grc.nia.nih.gov

Contact: beckerk@grc.nia.nih.gov
Coming Full Circle: The Study of Big Business since 1950
Authors: Klein Maury
Published: July 2002

Taking a broad view of historians' work on the rise of big business in the United States over the last half-century, this article attempts to assess both where business history has been and where it may go in the future. The analysis recognizes the centrality of the impact made by Alfred D. Chandler, Jr., but it also delves into other paths, including some not taken, of interest to historians. This wide-ranging interpretation also maintains the importance of big business itself as a subject worthy of historical attention and argues that its crucial role in the development of American society has not yet been considered by mainstream historians with the intensity it deserves. Musing over the nearly constant preoccupation of practitioners with defining the scope of business history as a field, the essay highlights a number of topics needing attention, suggesting that historians of business are well positioned to shed light on the growing role of business in all aspects of life in the twenty-first century.
The molecular basis of ethylene signalling inArabidopsis
Authors: Woeste Keith , Kieber Joseph J.
Published: July 2002

The simple gas ethylene profoundly influences plants at nearly every stage of growth and development. In the past ten years, the use of a genetic approach, based on the triple response phenotype, has been a powerful tool for investigating the molecular events that underlie these effects. Several fundamental elements of the pathway have been described: a receptor with homology to bacterial two–component histidine kinases (ETR1), elements of a MAP kinase cascade (CTR1) and a putative transcription factor (EIN3). Taken together, these elements can be assembled into a simple, linear model for ethylene signalling that accounts for most of the well–characterized ethylene mediated responses.
Androgen receptor mutation in Kennedy'sdisease
Authors: Fischbeck Kenneth H. , Lieberman Andrew , Bailey Christine K. , Abel Annette , Merry Diane E.
Published: July 2002

Kennedy'sdisease is an X–linked form of motor neuron disease caused by an expanded polyglutamine repeat in the androgen receptor. While the expansion mutation causes some loss of transcriptional activity by the androgen receptor, the predominant effect of expansion is probably a toxic gain of function, similar to the mechanism of other polyglutamine expansion diseases. Features of the neurodegenerative phenotype of Kennedy'sdisease have now been reproduced in transgenic animals and neuronal cell culture. Nuclear inclusions of mutant androgen receptor protein are found in these model systems and in autopsy samples from patients with Kennedy'sdisease.
Modeling the transmembrane domain of bacterial chemoreceptors
Authors: Peach Megan L. , Hazelbauer Gerald L. , Lybrand Terry P.
Published: July 2002

Bacterial chemoreceptors signal across the membrane by conformational changes that traverse a four‐helix transmembrane domain. High‐resolution structures are available for the chemoreceptor periplasmic domain and part of the cytoplasmic domain but not for the transmembrane domain. Thus, we constructed molecular models of the transmembrane domains of chemoreceptors Trg and Tar, using coordinates of an unrelated four‐helix coiled coil as a template and the X‐ray structure of a chemoreceptor periplasmic domain to establish register and positioning. We tested the models using the extensive data for cross‐linking propensities between cysteines introduced into adjacent transmembrane helices, and we found that many aspects of the models corresponded with experimental observations. The one striking disparity, the register of transmembrane helix 2 (TM2) relative to its partner transmembrane helix 1, could be corrected by sliding TM2 along its long axis toward the periplasm. The correction implied that axial sliding of TM2, the signaling movement indicated by a large body of data, was of greater magnitude than previously thought. The refined models were used to assess effects of inter‐helical disulfides on the two ligand‐induced conformational changes observed in alternative crystal structures of periplasmic domains: axial sliding within a subunit and subunit rotation. Analyses using a measure of disulfide potential energy provided strong support for the helical sliding model of transmembrane signaling but indicated that subunit rotation could be involved in other ligand‐induced effects. Those analyses plus modeled distances between diagnostic cysteine pairs indicated a magnitude for TM2 sliding in transmembrane signaling of several angstroms.
Liquid–vapor equilibrium in a gravitational field
Authors: Berberan-Santos Mário N. , Bodunov Evgeny N. , Pogliani Lionello
Published: July 2002

The effect of a constant gravitational field on the existence and position of the liquid–vapor boundary of a pure classical fluid is quantitatively discussed on the basis of two simple models: (a) a perfect gas and incompressible liquid model, and (b) a van der Waals fluid model. The van der Waals equation is used as a function of reduced parameters, and it is shown that two dimensionless parameters suffice to describe the vertical concentration profile and the liquid–vapor boundary position. With this model, it is shown how the gravitational field induces a vertical phase separation, an observation so common that it is usually taken for granted but not modeled. The conditions for a gravitational field to produce gas condensation are also discussed.
Blast noise propagation above a snow cover
Authors: Albert Donald G. , Hole Lars R.
Published: July 2002

A porous medium model of a snow cover, rather than a viscoelastic treatment, has been used to simulate measured, horizontally traveling acoustic waveform propagation above a dry snow cover 11–20 cm thick. The waveforms were produced by explosions of 1-kg charges at propagation distances of 100 to 1400 m. These waveforms, with a peak frequency around 30 Hz, show pulse broadening effects similar to those previously seen for higher-frequency waves over shorter propagation distances. A rigid-ice-frame porous medium (“rigid-porous”) impedance model, which includes the effect of the pores within the snow but ignores any induced motion of the ice particles, is shown to produce much better agreement with the measured waveforms compared with a viscoelastic solid treatment of the snow cover. From the acoustic waveform modeling, the predicted average snow cover depth of 18 cm and effective flow resistivities of 16–31 kPa s m−2 agree with snow pit observations and with previous acoustic measurements over snow. For propagation in the upwind direction, the pulse broadening caused by the snow cover interaction is lessened, but the overall amplitude decay is greater because of refraction of the blast waves.
Spatial unmasking of nearby speech sources in a simulated anechoic environment
Authors: Shinn-Cunningham Barbara G. , Schickler Jason , Kopčo Norbert , Litovsky Ruth
Published: July 2002

Spatial unmasking of speech has traditionally been studied with target and masker at the same, relatively large distance. The present study investigated spatial unmasking for configurations in which the simulated sources varied in azimuth and could be either near or far from the head. Target sentences and speech-shaped noise maskers were simulated over headphones using head-related transfer functions derived from a spherical-head model. Speech reception thresholds were measured adaptively, varying target level while keeping the masker level constant at the “better” ear. Results demonstrate that small positional changes can result in very large changes in speech intelligibility when sources are near the listener as a result of large changes in the overall level of the stimuli reaching the ears. In addition, the difference in the target-to-masker ratios at the two ears can be substantially larger for nearby sources than for relatively distant sources. Predictions from an existing model of binaural speech intelligibility are in good agreement with results from all conditions comparable to those that have been tested previously. However, small but important deviations between the measured and predicted results are observed for other spatial configurations, suggesting that current theories do not accurately account for speech intelligibility for some of the novel spatial configurations tested.
Timing interference to speech in altered listening conditions
Authors: Howell Peter , Sackin Stevie
Published: July 2002

A theory is outlined that explains the disruption that occurs when auditory feedback is altered. The key part of the theory is that the number of, and relationship between, inputs to a timekeeper, operative during speech control, affects speech performance. The effects of alteration to auditory feedback depend on the extra input provided to the timekeeper. Different disruption is predicted for auditory feedback that is out of synchrony with other speech activity (e.g., delayed auditory feedback, DAF) compared with synchronous forms of altered feedback (e.g., frequency shifted feedback, FSF). Stimulus manipulations that can be made synchronously with speech are predicted to cause equivalent disruption to the synchronous form of altered feedback. Three experiments are reported. In all of them, subjects repeated a syllable at a fixed rate (Wing and Kristofferson, 1973). Overall timing variance was decomposed into the variance of a timekeeper (Cv) and the variance of a motor process (Mv). Experiment 1 validated Wing and Kristofferson’s method for estimating Cv in a speech task by showing that only this variance component increased when subjects repeated syllables at different rates. Experiment 2 showed DAF increased Cv compared with when no altered sound occurred (experiment 1) and compared with FSF. In experiment 3, sections of the subject’s output sequence were increased in amplitude. Subjects just heard this sound in one condition and made a duration decision about it in a second condition. When no response was made, results were like those with FSF. When a response was made, Cv increased at longer repetition periods. The findings that the principal effect of DAF, a duration decision and repetition period is on Cv whereas synchronous alterations that do not require a decision (amplitude increased sections where no response was made and FSF) do not affect Cv, support the hypothesis that the timekeeping process is affected by synchronized and asynchronized inputs in different ways.
Focusing of N waves in air by an ellipsoidal reflector
Authors: Wright Wayne M. , Blackstock David T.
Published: July 2002

An experimental investigation of the focusing of intense, airborne pressure pulses by an ellipsoidal reflector is reported. Short-duration N waves were generated by weak sparks at the near focus F1 of four different prolate ellipsoidal surfaces. Reflection then concentrated the rays at the far focus F2. Measurements were made with a wide-band microphone, primarily along the axis of the reflector. A few transverse measurements in the plane of F2 were also made. In the axial measurements the reflected (upright N wave) and edge-diffracted (inverted N wave) components of the signal are distinct at points distant from F2, approach each other as the focus is neared, and merge at the focus. At the focus the waveform is U-shaped, or cusped. Beyond F2 a “droopy” N wave emerges and, where the edge wave can be resolved, it now arrives first and is phase inverted relative to its prefocal version. The more intense reflected wave does not experience phase inversion. Some features of the observed waveforms are consistent with recent calculations by Hamilton, which are based on lossless, linear theory. Other wave characteristics, including pulse amplitude and location of the head and tail shocks, are strongly influenced by nonlinear effects.
Tomographic inversion of geoacoustic properties in a range-dependent shallow water environment
Authors: Pignot Patrick , Chapman Ross
Published: July 2002

This paper presents a matched-field tomography method to estimate the geoacoustic properties of the ocean bottom for a range-dependent medium in shallow water. The inversion method has been developed in order to process experimental data recorded during the Haro Strait PRIMER trial. This experiment was carried out in June 1996 and used low-frequency broadband signals that were received on three vertical line arrays. The data inversion is particularly difficult in this experiment because of the complex bathymetry of the experimental site. For this inversion, a range-dependent ray code has first been developed to solve the forward problem allowing an arbitrarily layered bottom environment. The inverse scheme is based on the propagation time and the amplitude of the recorded data and a simple new cost function is proposed. The significant feature of the inversion scheme is the division of the process into a series of layers. Starting with the topmost layer, the range-dependent thickness, sound speed, and density are estimated via a Monte Carlo method. Inversion results are presented on synthetic and experimental data. [Work supported by the Office of Naval Research.]
Getting two birds with one phone: An acoustic sensor for both speech recognition and medical monitoring
Authors: Bass James D. , Scanlon Michael V. , Mills Thomas K.
Published: July 2002

Automatic speech recognition (ASR) in noisy environments requires innovative use of disparate technology to overcome the special demands caused by multiple speakers and minimal signal-to-noise ratios (SNRs). Use of nonairborne acoustic sensors for ASR imposes special requirements on speech engines due to the changes in spectral information caused by alternative pickup locations. Specifically, the relative power of voiced and nonvoiced components is often reversed when compared to the relative power of these components collected with conventional microphone technology. Our research entails the evaluation of various ASR sampling configurations in conjunction with different body location points for the physiological sensor. Physiology provides clues to speakers’ stress or cognition. For ASR, our goal is to build a suite of optimal sampling configurations for several strategic body locations (e.g., throat temple, thorax, etc.). The experimental design includes traditional word error rate and subjective task completion components. These experiments were conducted in environments with SNR ranges of 10, 3, 0, and −1 dB. These SNR ranges cover the optimal commercial ASR environment of 10 dB to ranges where commercial ASR systems with conventional microphone technology are completely ineffective. Pilot studies indicate good performance below 0-dB SNR for a sensor that is throat located.
Phonemic effects in spoken-word recognition in Japanese
Authors: Cutler Anne , Otake Takashi
Published: July 2002

Previous studies have shown that Japanese listeners are sensitive to the moraic structure of speech, and find it easier to manipulate or respond to morae than phonemes. We further examined moraic processing via two word reconstruction experiments, in which Japanese listeners heard three- or four-mora nonwords which could be changed into real words by substitution of a single mora. In experiment 1, listeners had to change the first mora of the nonword, in experiment 2 the final mora. We compared three types of substitution for CV morae: substitution preserving the C (e.g., kimera or kamere for, respectively, the first and last mora of the word kamera, which has three morae: ka-me-ra), substitution preserving V (namera, kamena), or substitution preserving neither (nimera, kamene). When C or V was preserved, responses were significantly faster and more accurate than when neither was preserved. In initial position, there was no difference between C- and V-preserving substitutions, but in final position, preservation of the C led to faster and more accurate responses than preservation of the V. These results confirm that spoken word recognition in Japanese is sensitive to vocabulary structure and similarity (inter alia at a submoraic level) between words.
Methods and applications of time–frequency analysis
Authors: Loughlin Patrick J.
Published: July 2002

Time–frequency analysis is a common technique for studying signals whose spectral characteristics change over time, the principal method being the short-time Fourier transform or spectrogram. In the past decade, the theory and methods of time–frequency analysis have witnessed extensive development and application, due to the effective use of Cohen’s general formulation for time–frequency distributions. These methods have been found to be useful in a variety of areas, including acoustic scattering, biological signal analysis, and machine vibration analysis, among many others. A key development has been an understanding of the conditional moments of the distribution and their link to physical attributes of the signal such as its amplitude and phase. A review of the theory and methods of time–frequency analysis is presented, with an emphasis on applications in a variety of areas. [Work supported by ONR N00014-98-1-0680.]
The elastic extension of polymer fibers in the glassy state: Experimental results
Authors: Baltussen J. J. M. , Northolt M. G.
Published: July 2002

The results of the continuous chain model for the elastic deformation of polymer fibers in the glassy state, which has been presented in the previous article, are compared to the results from experiments on poly(p-phenylene terephthalamide) (PpPTA), poly(ethylene terephthalate) (PET), cellulose, and PE fibers, and PpPTA and PET sheets. The calculated elastic stress versus strain curve is compared to the experimental curve of PpPTA fibers. The predicted relation between the elastic modulus versus strain curve and the orientation of the fiber during extension are compared to the results obtained by x-ray diffraction. The effect of plastic deformation on the experimental modulus versus strain curve is considered, and a new method for the experimental determination of the shear modulusg from the elastic modulus versus strain curve is presented. The calculated elastic modulus versus strain curves are compared to the experimental curves of PpPTA, PET, cellulose, and PE fibers with widely divergent values for their orientation parameter. The shear moduli for these fibers have been determined and are compared with literature values, the relation between the experimentally determined shear modulus and the structure of the fiber is discussed. The shear moduli of a series of PET fibers are compared to the values obtained by birefringence. The modulus of PpPTA and PET sheets are compared to the calculated values. Good agreement between the experimental and calculated results has been obtained.
Powder X-ray diffraction data for potassium silver thiocyanate, AgK(SCN)2 and dipotassium silver thiocyanate, AgK2(SCN)3
Authors: Güneş Minna , Lahtinen Manu , Valkonen Jussi
Published: July 2002

Previously unpublished powder X-ray diffraction data for potassium silver thiocyanate, AgK(SCN)2 and dipotassium silver thiocyanate, AgK2(SCN)3 are presented. F30 values for AgK(SCN)2 and AgK2(SCN)3 are 80(0.0075, 50) and 53(0.0089, 63), respectively. The Rietveld refinement of the patterns is also performed. For AgK(SCN)2Rp=6.98, Rwp=11.84, and RBragg=2.9. For AgK2(SCN)3Rp=7.22, Rwp=10.79, and RBragg=5.0.
RNA cytosine methyltransferase NSUN5 promotes protein synthesis and tumorigenic phenotypes in glioblastoma
Authors: Zhou Jiesi , Kong Yan Shu , Vincent Krista M. , Dieters‐Castator Dylan , Bukhari Amirali B. , Glubrecht Darryl , Liu Rong‐Zong , Quilty Douglas , Findlay Scott D. , Huang Xiaowei , Xu Zhihua , Yang Rui Zhe , Zhang Lanyue , Tang Emily , Lajoie Gilles , Eisenstat David D. , Gamper Armin M. , Fahlman Richard , Godbout Roseline , Postovit Lynne‐Marie , Fu YangXin
Published: April 2023

Glioblastoma (GBM) is the most common and aggressive malignant primary brain tumor in adults. The standard treatment achieves a median overall survival for GBM patients of only 15 months. Hence, novel therapies based on an increased understanding of the mechanistic underpinnings of GBM are desperately needed. In this study, we show that elevated expression of 28S rRNA (cytosine‐C(5))‐methyltransferase NSUN5, which methylates cytosine 3782 of 28S rRNA in GBM cells, is strongly associated with the poor survival of GBM patients. Moreover, we demonstrate that overexpression of NSUN5 increases protein synthesis in GBM cells. NSUN5 knockdown decreased protein synthesis, cell proliferation, sphere formation, migration, and resistance to temozolomide in GBM cell lines. NSUN5 knockdown also decreased the number and size of GBM neurospheres in vitro. As a corollary, mice harboring U251 tumors wherein NSUN5 was knocked down survived longer than mice harboring control tumors. Taken together, our results suggest that NSUN5 plays a protumorigenic role in GBM by enabling the enhanced protein synthesis requisite for tumor progression. Accordingly, NSUN5 may be a hitherto unappreciated target for the treatment of GBM.
Relationship between anticancer sensitivities and cellular respiration properties in 5‐fluorouracil‐resistant HCT116 human colorectal cancer cells
Authors: Kurasaka Chinatsu , Nishizawa Nana , Uozumi Haruka , Ogino Yoko , Sato Akira
Published: April 2023

5‐Fluorouracil (5‐FU) is widely used for colorectal cancer (CRC) treatment; however, continuous treatment of CRC cells with 5‐FU can result in acquired resistance, and the underlying mechanism of 5‐FU resistance remains unclear. We previously established an acquired 5‐FU‐resistant CRC cell line, HCT116RF10, and examined its biological features and 5‐FU resistance mechanisms. In this study, we evaluated the 5‐FU sensitivity and cellular respiration dependency of HCT116RF10 cells and parental HCT116 cells under conditions of high‐ and low‐glucose concentrations. Both HCT116RF10 and parental HCT116 cells were more sensitive to 5‐FU under low‐glucose conditions compared with high‐glucose conditions. Interestingly, HCT116RF10 and parental HCT116 cells exhibited altered cellular respiration dependence for glycolysis and mitochondrial respiration under high‐ and low‐glucose conditions. Additionally, HCT116RF10 cells showed a markedly decreased ATP production rate compared with HCT116 cells under both high‐ and low‐glucose conditions. Importantly, glucose restriction significantly reduced the ATP production rate for both glycolysis and mitochondrial respiration in HCT116RF10 cells compared with HCT116 cells. The ATP production rates in HCT116RF10 and HCT116 cells were reduced by approximately 64% and 23%, respectively, under glucose restriction, suggesting that glucose restriction may be effective at enhancing 5‐FU chemotherapy. Overall, these findings shed light on 5‐FU resistance mechanisms, which may lead to improvements in anticancer treatment strategies.
Aquaporin‐Based Biomimetic Membranes for Low Energy Water Desalination and Separation Applications
Authors: Azarafza Abouzar , Islam Muhammad Amirul , Golpazirsorkheh Yekta , Efteghar Irene , Sadrzadeh Mohtada , Kamkar Milad , Shojaei Arsalan Faghih , Younas Mohammad , Aminabhavi Tejraj M. , Rezakazemi Mashallah
Published: April 2023

The emergence of biomimetic materials developed using nature's inspiration and biological domains can drive a paradigm shift in the design and operation of future‐generation materials in separation applications. In recent years, biomimetic membranes have drawn interest of many researchers for water treatment applications. Among the biomimetic membranes, protein‐based membranes, specifically those synthesized by aquaporin, have received much attention in recent years due to their high osmotic water permeability and excellent ability to remove small molecules, thereby overcoming the trade‐off between the water flux and the contaminant's rejection. The separation efficiency and fouling properties are significantly improved by taking advantage of the strategies evolved in nature. This review provides a comprehensive overview of the state‐of‐the‐art aquaporin‐based biomimetic membranes (ABMs), mainly focusing on their synthesis, characterization, and performance as selective layer in composite membranes for reverse osmosis, nanofiltration, and forward osmosis for water desalination. Fabrication methods and characterization techniques of ABMs and their performance in water desalination are also reviewed, while the main obstacles for their successful commercial viability in wastewater treatment are provided. The applications of ABMs in various separation processes other than water desalination and their potential market are presented to inspire future researchers in this versatile area.
Recent Advances in Nanomaterials‐Based FETs for SARS‐CoV‐2 (COVID‐19 Virus) Diagnosis
Authors: Aftab Sikandar , Iqbal Muhammad Zahir , Hussain Sajjad , Hegazy Hosameldin Helmy
Published: April 2023

The emergence of infectious diseases that are quickly spreading, like the coronavirus (COVID‐19), necessitates the development of efficient biosensors that can quickly detect and identify pathogens. It is essential to create sensitive virus detection methods in order to stop a virus from spreading throughout the world. It is determined that field‐effect transistors (FETs) made of nanomaterials are potential candidates for rapid virus identification due to how easily the electronic transport characteristics of such an atomically thin nanomaterial can be affected by perturbations. Various FETs in this review article are investigated that are based on nanoparticles, carbon nanotubes (CNT), graphene, graphene‐oxide, and semiconducting transition metal dichalcogenides (TMDs) WSe2in order to show that they are promising biosensors in regards to quickly and precisely detect COVID‐19. The conjugation of nanomaterials with proteins enables the direct delivery of antiviral agents to the host cells. This method also minimizes the off‐target effects and enables the targeted interactions. This mechanism has produced encouraging results in regards to sensing or treating COVID‐19. The high surface area and extremely small size of nanomaterials make them crucial in regards to the development of new detection methods. The point‐of‐care test method of detection is quick, simple, and user‐friendly, and it only requires a small amount of a patient's blood. It does not require a laboratory or trained professionals. This overview of the current research that is conducted on nanomaterials will prove to be useful in the process of formulating strategies for the diagnosis, treatment, and vaccination of viruses in opinion. Finally, the conclusion of this review provides a summary of the current challenges and the future prospects.
Bioprinting of Stem Cell Spheroids Followed by Post‐Printing Chondrogenic Differentiation for Cartilage Tissue Engineering
Authors: Decarli Monize Caiado , Seijas‐Gamardo Adrián , Morgan Francis L. C. , Wieringa Paul , Baker Matthew B. , Silva Jorge Vicente L. , Moraes Ângela Maria , Moroni Lorenzo , Mota Carlos
Published: April 2023

Cartilage tissue presents low self‐repair capability and lesions often undergo irreversible progression. Structures obtained by tissue engineering, such as those based in extrusion bioprinting of constructs loaded with stem cell spheroids may offer valuable alternatives for research and therapeutic purposes. Human mesenchymal stromal cell (hMSC) spheroids can be chondrogenically differentiated faster and more efficiently than single cells. This approach allows obtaining larger tissues in a rapid, controlled and reproducible way. However, it is challenging to control tissue architecture, construct stability, and cell viability during maturation. Herein, this work reports a reproducible bioprinting process followed by a successful post‐bioprinting chondrogenic differentiation procedure using large quantities of hMSC spheroids encapsulated in a xanthan gum‐alginate hydrogel. Multi‐layered constructs are bioprinted, ionically crosslinked, and post chondrogenically differentiated for 28 days. The expression of glycosaminoglycan, collagen II and IV are observed. After 56 days in culture, the bioprinted constructs are still stable and show satisfactory cell metabolic activity with profuse extracellular matrix production. These results show a promising procedure to obtain 3D models for cartilage research and ultimately, an in vitro proof‐of‐concept of their potential use as stable chondral tissue implants.
A Novel Patient‐Personalized Nanovector Based on Homotypic Recognition and Magnetic Hyperthermia for an Efficient Treatment of Glioblastoma Multiforme
Authors: De Pasquale Daniele , Pucci Carlotta , Desii Andrea , Marino Attilio , Debellis Doriana , Leoncino Luca , Prato Mirko , Moscato Stefania , Amadio Simone , Fiaschi Pietro , Prior Alessandro , Ciofani Gianni
Published: April 2023

Glioblastoma multiforme (GBM) is the deadliest brain tumor, characterized by an extreme genotypic and phenotypic variability, besides a high infiltrative nature in healthy tissues. Apart from very invasive surgical procedures, to date, there are no effective treatments, and life expectancy is very limited. In this work, an innovative therapeutic approach based on lipid‐based magnetic nanovectors is proposed, owning a dual therapeutic function: chemotherapy, thanks to an antineoplastic drug (regorafenib) loaded in the core, and localized magnetic hyperthermia, thanks to the presence of iron oxide nanoparticles, remotely activated by an alternating magnetic field. The drug is selected based on ad hoc patient‐specific screenings; moreover, the nanovector is decorated with cell membranes derived from patients’ cells, aiming at increasing homotypic and personalized targeting. It is demonstrated that this functionalization not only enhances the selectivity of the nanovectors toward patient‐derived GBM cells, but also their blood–brain barrier in vitro crossing ability. The localized magnetic hyperthermia induces both thermal and oxidative intracellular stress that lead to lysosomal membrane permeabilization and to the release of proteolytic enzymes into the cytosol. Collected results show that hyperthermia and chemotherapy work in synergy to reduce GBM cell invasion properties, to induce intracellular damage and, eventually, to prompt cellular death.
Oxygen‐Vacancy‐Rich Piezoelectric BiO2−x Nanosheets for Augmented Piezocatalytic, Sonothermal, and Enzymatic Therapies
Authors: Yang Lu , Tian Boshi , Xie Ying , Dong Shuming , Yang Meiqi , Gai Shili , Lin Jun
Published: April 2023

Piezocatalytic therapy is a new‐emerging reactive oxygen species (ROS)‐enabled therapeutic strategy that relies on built‐in electric field and energy‐band bending of piezoelectric materials activated by ultrasound (US) irradiation. Despite becoming a hot topic, material development and mechanism exploration are still underway. Herein, as‐synthesized oxygen‐vacancy‐rich BiO2−x nanosheets (NSs) demonstrate outstanding piezoelectric properties. Under US, a piezo‐potential of 0.25 V for BiO2−x NSs is sufficient to tilt the conduction band to be more negative than the redox potentials of O2/•O2−, •O2−/H2O2, and H2O2/•OH, which initiates a cascade reaction for ROS generation. Moreover, the BiO2−x NSs exhibit peroxidase and oxidase‐like activities to augment ROS production, especially in the H2O2‐overexpressed tumor microenvironment. Density functional theory calculations show that the generated oxygen vacancies in BiO2−x NSs are favorable for H2O2 adsorption and increasing the carrier density to produce ROS. Furthermore, the quick movement of electrons enables an excellent sonothermal effect, for example, rapid rise in temperature to nearly 65 °C upon US with low power (1.2 W cm−2) and short time (96 s). Therefore, this system realizes a multimode synergistic combination of piezocatalytic, enzymatic, and sonothermal therapies, providing a new direction for defect engineering‐optimized piezoelectric materials for tumor therapy.
Nano Surface‐Heterogeneities of Particles Modulate the Macroscopic Properties of Hydrogels
Authors: Rana Vijay K. , Karami Peyman , Nasrollahzadeh Naser , Pioletti Dominique P.
Published: April 2023

Nanoparticles, when incorporated into polymer matrices, can improve the intrinsic properties of composite materials. These materials possess fascinating properties and find widespread applications in bioengineering, medicine, aerospace, and electronics. However, the impact of nanoparticle surface heterostructures on composite systems is not fully understood. To bridge this gap, composite hydrogels (HRCs) are developed using rough‐surfaced raspberry‐like colloidal (RC) particles. It is hypothesized that the surface roughness of nanoparticles can significantly affect their adsorption, motion, and interfacial forces when interacting with polymeric networks, thereby influencing the macroscopic properties of HRCs. The properties of HRCs are compared with those of composite hydrogels containing smooth‐surfaced particles (HSCs) to isolate the effect of surface roughness. The results show that the nano‐surface heterogeneities of nanoparticles dictate the macroscopic properties of HRC hydrogels. It is found that HRCs exhibit much greater mechanical and adhesive properties compared to HSCs and control hydrogel without nanoparticles. As identified by the relaxation behavior, the enhanced frictional drag of interstitial fluid due to surface roughness, combined with the strong interaction of polymer network components dynamically linked by rough‐surfaced RC particles, is responsible for these improvements. These findings can guide the design and fabrication of new nanocomposites, including hydrogels, for various applications.
Alkyl Chain Length‐Dependent Amine‐Induced Crystallization for Efficient Interface Passivation of Perovskite Solar Cells
Authors: Zhao Pengjun , Subbiah Jegadesan , Zhang Bolong , Hutchison James A. , Ahluwalia Gagandeep , Mitchell Valerie , Ghiggino Kenneth P. , Jones David J.
Published: April 2023

Efficient surface passivation of perovskite solar cells (PSC) using treatment with ammonium salts is demonstrated as an efficient method to enhance the device performance, owing to the affinity between the amine group and [PbI6]4− octahedron. However, due to their high solubility in polar solvents (DMF/DMSO), ammonium salts are more difficult to use in passivation of the interface between the electron transport layer and perovskite thin film in n‐i‐p structured PSCs. In this report, this work successfully links the amine group with a fullerene through a series of increasing carbon chain length, from two to twelve methylene units (FC‐X, X = 2, 6, 12), and then introduce the synthesized molecules as interface passivation layers into SnO2‐based planar n‐i‐p PSCs. Results show that the interface passivation effect is highly dependent on the side‐chain length, and the longer chain length amine‐functionalized fullerene is more beneficial for the device performance. A power conversion efficiency as high as 21.2% is achieved by using FC‐12. The surface energy, perovskite crystallite size and electron transfer capacity correlate with the linker chain length. This work develops an amine‐induced anchored crystallization of perovskite to unravel the mechanism of this passivation effect. As expected, enhanced device stability is also observed in the FC‐12 passivated PSCs.
Highly Efficient Electrocatalytic Hydrogen Production over Carbon Nanotubes Loaded with Platinum Nanoparticles Using Solution Processing
Authors: Metawea Osama R. M. , Nara Miyuki , Murakami Takeharu , Wada Satoshi , Fujii Katsushi , Ito Yoshihiro , Kawamoto Masuki
Published: April 2023

Proton exchange membrane (PEM) electrolyzers are used for hydrogen (H2) production by water electrolysis. The commercial cathodic electrocatalyst for this process is typically mechanically mixed platinum on carbon (Pt/C). However, aggregation of the platinum (Pt) makes high loading of the catalyst difficult. Therefore, a method for the homogeneous combination of Pt and carbon materials is required. Herein, the first example of a highly efficient single‐walled carbon nanotube (SWCNT) cathodic H2‐production electrocatalyst that is loaded with platinum nanoparticles (PtNPs) using a newly developed suspension method is reported. Combining SWCNTs lapped with a water‐soluble, thiol‐functionalized polymer with PtNPs in water yields a PtNP‐conjugated SWCNT suspension. The electrocatalyst exhibits a low overpotential of 47 mV at a current density of 10 mA cm−2 toward H2 evolution in 0.5 m sulfuric acid. A PEM electrolyzer fabricated using the optimally prepared electrocatalyst with the low loading of 15 µgPt cm−2 shows a high mass activity of 27 200 A gPt−1, which is 80 times that of Pt/C with a loading amount of 2.8 mgPt cm−2 (324 A gPt−1). In addition, the PEM electrolyzer produces H2 at a Faradaic efficiency of 97% and operates stably for 150 h at 100 mA cm−2.
Multiple Shapes Micro‐LEDs with Defect Free Sidewalls and Simple Liftoff and Transfer Using Selective Area Growth on Hexagonal Boron Nitride Template
Authors: Gujrati Rajat , Srivastava Ashutosh , Vuong Phuong , Ottapilakkal Vishnu , Sama Yves N. , Ngo Thi Huong , Moudakir Tarik , Patriarche Gilles , Gautier Simon , Voss Paul L. , Sundaram Suresh , Salvestrini Jean Paul , Ougazzaden Abdallah
Published: April 2023

Several technological challenges have prevented GaN‐based micro‐LEDs from finding application in mass market displays, despite their unique properties such as very high brightness and the very fast response time of GaN‐based materials. The primary challenges are the cost and complexity of lift‐off and transfer of LEDs from sapphire substrates to suitable supports as well as the lowered performance of tiny micro‐LEDs caused by chemical etching that defines individual LEDs. Herein, this work reports demonstration of a complete process that solves these challenges with epitaxy and cleanroom technologies that are commercially available. The process begins with van der Waals epitaxy of 2D h‐BN on silica masks with square, triangular and hexagonal patterns on sapphire substrates which define the micro‐LED regions. Then selective area growth of MQW LED heterostructures, with ultra smooth crystalline sidewalls, down to ultra tiny size of 1.4 µm is performed. Because of the lack of vertical chemical bonds in the h‐BN layer, simple mechanical lift‐off and transfer is performed on an array of LEDs heterostructures down to size of 8 µm. Finally, transparent ITO p‐contacts are deposited on LEDs with uniform lift‐off, resulting in high brightness LEDs.
A Mobile E‐Nose Prototype for Online Breath Analysis
Authors: Chen Qiaofen , Guo Xufeng , Jiang Yuyue , Liu Xuemei , Xu Shiyuan , Huang Xuqing , Chen Yueling , Ye Xiaogang , Pan Aiwu , Dong Yalin , He Zhengfu , Wu Jianmin
Published: April 2023

Exhaled breath provides information of individual's holistic physiological condition, making non‐invasive exhaled breath testing a convenient and effective choice for personalized health management. This work proposes a mobile e‐nose prototype equipped with a miniaturized gas delivering unit, an advanced sensor array, a customized analog to digital conversion circuit board, an online data transmission, and machine learning algorithms that can effectively detect and analyze volatile compounds in exhaled breath, providing a systematic design strategy for non‐invasive disease diagnosis. The gas sensor array, as a core element, is composed of eight graphene‐based chemiresistive materials which are sensitive to trace gas analytes. In an online breath test study with 401 cases, patients with respiratory diseases can be distinguished from the healthy with an overall accuracy higher than 80%. In addition, classification of breath samples between patients with chronic obstructive pulmonary disease and the healthy higher than 85% is achieved. These results indicate the proposed portable e‐nose prototype holds great promise in personalized health state monitoring.