bluuebunny/crossref_metadata_2025 huggingface dataset:
Early Assembly Step of a Retroviral Envelope Glycoprotein: Analysis Using a Dominant Negative Assay
Authors: Rosenberg Arielle R. , Delamarre Lélia , Pique Claudine , Le Blanc Isabelle , Griffith Graziella , Dokhélar Marie-Christine
Published: July 2002

As for most integral membrane proteins, the intracellular transport of retroviral envelope glycoproteins depends on proper folding and oligomeric assembly in the ER. In this study, we considered the hypothesis that a panel of 22 transport-defective mutants of the human T cell leukemia virus type 1 envelope glycoprotein might be defective in ER assembly. Upon cell cotransfection with wild-type envelope, however, the vast majority of these transport-defective mutants (21 of 22) exerted a specific trans-dominant negative effect. This effect was due to random dimerization of the mutated and wild-type glycoproteins that prevented the intracellular transport of the latter. This unexpected result suggests that association of glycoprotein monomers precedes the completion of folding. The only mutation that impaired this early assembly was located at the NH2 terminus of the protein. COOH-terminally truncated, soluble forms of the glycoprotein were also trans-dominant negative provided that their NH2 terminus was intact. The leucine zipper-like domain, although involved in oligomerization of the envelope glycoproteins at the cell surface, did not contribute to their intracellular assembly. We propose that, at a step subsequent to translation, but preceding complete folding of the monomers, glycoproteins assemble via their NH2-terminal domains, which, in turn, permits their cooperative folding.
Inhibitory Role of α6β4-Associated Erbb-2 and Phosphoinositide 3-Kinase in Keratinocyte Haptotactic Migration Dependent on α3β1 Integrin
Authors: Hintermann Edith , Bilban Martin , Sharabi Andrew , Quaranta Vito
Published: July 2002

Keratinocytes and other epithelial cells express two receptors for the basement membrane (BM) extracellular matrix component laminin-5 (Ln-5), integrins α3β1 and α6β4. While α3β1 mediates adhesion, spreading, and migration (Kreidberg, J.A. 2000. Curr. Opin. Cell Biol. 12:548–553), α6β4 is involved in BM anchorage via hemidesmosomes (Borradori, L., and A. Sonnenberg. 1999. J. Invest. Dermatol. 112:411–418). We investigated a possible regulatory interplay between α3β1 and α6β4 in cell motility using HaCaT keratinocytes as a model. We found that α6β4 antibodies inhibit α3β1-mediated migration on Ln-5, but only when migration is haptotactic (i.e., spontaneous or stimulated by α3β1 activation), and not when chemotactic (i.e., triggered by epidermal growth factor receptor). Inhibition of migration by α6β4 depends upon phosphoinositide 3-kinase (PI3-K) since it is abolished by PI3-K blockers and by dominant-negative PI3-K, and constitutively active PI3-K prevents haptotaxis. In HaCaT cells incubated with anti–α6β4 antibodies, activation of PI3-K is mediated by α6β4-associated erbB-2, as indicated by erbB-2 autophosphorylation and erbB-2/p85 PI3-K coprecipitation. Furthermore, dominant-negative erbB-2 abolishes inhibition of haptotaxis by anti–α6β4 antibodies. These results support a model whereby (a) haptotactic cell migration on Ln-5 is regulated by concerted action of α3β1 and α6β4 integrins, (b) α6β4-associated erbB-2 and PI3-K negatively affect haptotaxis, and (c) chemotaxis on Ln-5 is not affected by α6β4 antibodies and may require PI3-K activity. This model could be of general relevance to motility of epithelial cells in contact with BM.
Drosophila Kelch regulates actin organization via Src64-dependent tyrosine phosphorylation
Authors: Kelso Reed J. , Hudson Andrew M. , Cooley Lynn
Published: July 2002

The Drosophila kelch gene encodes a member of a protein superfamily defined by the presence of kelch repeats. In Drosophila, Kelch is required to maintain actin organization in ovarian ring canals. We set out to study the actin cross-linking activity of Kelch and how Kelch function is regulated. Biochemical studies using purified, recombinant Kelch protein showed that full-length Kelch bundles actin filaments, and kelch repeat 5 contains the actin binding site. Two-dimensional electrophoresis demonstrated that Kelch is tyrosine phosphorylated in a src64-dependent pathway. Site-directed mutagenesis determined that tyrosine residue 627 is phosphorylated. A Kelch mutant with tyrosine 627 changed to alanine (KelY627A) rescued the actin disorganization phenotype of kelch mutant ring canals, but failed to produce wild-type ring canals. Electron microscopy demonstrated that phosphorylation of Kelch is critical for the proper morphogenesis of actin during ring canal growth, and presence of the nonphosphorylatable KelY627A protein phenocopied src64 ring canals. KelY627A protein in ring canals also dramatically reduced the rate of actin monomer exchange. The phenotypes caused by src64 mutants and KelY627A expression suggest that a major function of Src64 signaling in the ring canal is the negative regulation of actin cross-linking by Kelch.
Prevention of Peripheral Tolerance by a Dendritic Cell Growth Factor: Flt3 Ligand as an Adjuvant
Authors: Pulendran Bali , Smith J.L. , Jenkins M. , Schoenborn M. , Maraskovsky E. , Maliszewski C.R.
Published: July 2002

Injections of soluble proteins are poorly immunogenic, and often elicit antigen-specific tolerance. The mechanism of this phenomenon has been an enduring puzzle, but it has been speculated that tolerance induction may be due to antigen presentation by poorly stimulatory, resting B cells, which lack specific immunoglobulin receptors for the protein. In contrast, adjuvants, or infectious agents, which cause the release of proinflammatory cytokines such as tumor necrosis factor α and interleukin 1β in vivo are believed to recruit and activate professional antigen-presenting cells to the site(s) of infection, thereby eliciting immunity. Here we show that administration of Flt3 ligand (FL), a cytokine capable of inducing large numbers of dendritic cells (DCs) in vivo, (a) dramatically enhances the sensitivity of antigen-specific B and T cell responses to systemic injection of a soluble protein, through a CD40–CD40 ligand–dependent mechanism; (b) influences the class of antibody produced; and (c) enables productive immune responses to otherwise tolerogenic protocols. These data support the hypothesis that the delicate balance between immunity and tolerance in vivo is pivotally controlled by DCs, and underscore the potential of FL as a vaccine adjuvant for immunotherapy in infectious disease and other clinical settings.
Cure of Progressive Murine Leishmaniasis: Interleukin 4 Dominance Is Abolished by Transient CD4+ T Cell Depletion and T Helper Cell Type 1–selective Cytokine Therapy
Authors: Heinzel Frederick P. , Rerko Ronald M.
Published: July 2002

Progressive infection with Leishmania major in susceptible BALB/c mice is mediated by interleukin (IL)-4–producing T helper cell type 2 (Th2) CD4+ T cells that, once established, become resistant to Th1-deviating therapies with recombinant (r)IL-12 and/or neutralizing anti–IL-4 antibodies. We sought to restore protective immunity in advanced leishmaniasis by depletion of Th2-biased CD4+ populations and by cytokine-directed reconstitution of Th1 cellular responses during lymphocyte recovery. Treatment with cytolytic GK1.5 anti-CD4 mAb alone did not reverse disease in 3 wk–infected BALB/c mice, but GK1.5 combined with anti–IL-4 antibody and intralesional rIL-12 cured cutaneous lesions in 80% of mice and established a Th1-polarized cytokine response to L. major antigen protective against reinfection. The curative effects of GK1.5 were not replaced by cytotoxic anti-CD8 monoclonal antibody 2.43 or nondepleting anti-CD4 mAb YTS177, confirming that depletion of CD4+ cells was specific and essential for therapeutic effect. Finally, combined CD4+ depletion and IL-4 neutralization were curative, indicating that neither increased parasite burden nor altered accessory cell function independently biased towards Th2 reconstitution in advanced leishmaniasis. Advanced leishmaniasis can be cured by T cell depletion and cytokine-directed recovery of Th1 cellular responses, suggesting novel interventions for other immune-mediated diseases and identifying distinct roles for CD4+ T cell and non-T cell in the maintenance of Th2 and Th1 phenotypes.
XenopusCdc6 Performs Separate Functions in Initiating DNA Replication
Authors: Frolova Natalya S. , Schek Nancy , Tikhmyanova Nadia , Coleman Thomas R.
Published: July 2002

Cdc6 performs an essential role in the initiation of eukaryotic DNA replication by recruiting the minichromosome maintenance (MCM) complex onto DNA. Using immunodepletion/add-back experiments inXenopus egg extracts, we have determined that both Walker A (ATP binding) and Walker B (ATP hydrolysis) motifs ofXenopus Cdc6 (Xcdc6) are essential, but have distinct functional roles. Although Walker B mutant protein binds chromatin well, Walker A mutant protein binds chromatin poorly. Neither Walker A nor Walker B mutant protein, however, load appreciable MCM onto DNA. Herein, we provide evidence that Cdc6 functions as a multimer: 1) mutant and wild-type Xcdc6 form multimers; 2) either mutant protein is dominant negative when added before wild-type Xcdc6, but stimulates DNA replication when added simultaneously with wild-type Xcdc6; and 3) the two mutants restore DNA replication when added together, in the absence of wild-type Xcdc6. Our findings suggest that ATP may play a key regulatory role within this multimer: its binding to Cdc6 promotes chromatin association and its hydrolysis facilitates MCM loading. Moreover, ATP binding and hydrolysis may occur in transbetween Cdc6 subunits within the complex.
Identification and Characterization of ART-27, a Novel Coactivator for the Androgen Receptor N Terminus
Authors: Markus Steven M. , Taneja Samir S. , Logan Susan K. , Li Wenhui , Ha Susan , Hittelman Adam B. , Rogatsky Inez , Garabedian Michael J.
Published: July 2002

The androgen receptor (AR) is a ligand-regulated transcription factor that stimulates cell growth and differentiation in androgen-responsive tissues. The AR N terminus contains two activation functions (AF-1a and AF-1b) that are necessary for maximal transcriptional enhancement by the receptor; however, the mechanisms and components regulating AR transcriptional activation are not fully understood. We sought to identify novel factors that interact with the AR N terminus from an androgen-stimulated human prostate cancer cell library using a yeast two-hybrid approach designed to identify proteins that interact with transcriptional activation domains. A 157-amino acid protein termed ART-27 was cloned and shown to interact predominantly with the AR153–336, containing AF-1a and a part of AF-1b, localize to the nucleus and increase the transcriptional activity of AR when overexpressed in cultured mammalian cells. ART-27 also enhanced the transcriptional activation by AR153–336fused to the LexA DNA-binding domain but not other AR N-terminal subdomains, suggesting that ART-27 exerts its effect via an interaction with a defined region of the AR N terminus. ART-27 interacts with AR in nuclear extracts from LNCaP cells in a ligand-independent manner. Interestingly, velocity gradient sedimentation of HeLa nuclear extracts suggests that native ART-27 is part of a multiprotein complex. ART-27 is expressed in a variety of human tissues, including sites of androgen action such as prostate and skeletal muscle, and is conserved throughout evolution. Thus, ART-27 is a novel cofactor that interacts with the AR N terminus and plays a role in facilitating receptor-induced transcriptional activation.
Combining many multiple alignments in one improved alignment.
Authors: Bucka-Lassen K , Caprani O , Hein J
Published: July 2002

MOTIVATION: The fact that the multiple sequence alignment problem is of high complexity has led to many different heuristic algorithms attempting to find a solution in what would be considered a reasonable amount of computation time and space. Very few of these heuristics produce results that are guaranteed always to lie within a certain distance of an optimal solution (given a measure of quality, e.g. parsimony). Most practical heuristics cannot guarantee this, but nevertheless perform well for certain cases. An alignment, obtained with one of these heuristics and with a bad overall score, is not unusable though, it might contain important information on how substrings should be aligned. This paper presents a method that extracts qualitatively good sub-alignments from a set of multiple alignments and combines these into a new, often improved alignment. The algorithm is implemented as a variant of the traditional dynamic programming technique. RESULTS: An implementation of ComAlign (the algorithm that combines multiple alignments) has been run on several sets of artificially generated sequences and a set of 5S RNA sequences. To assess the quality of the alignments obtained, the results have been compared with the output of MSA 2.1 (Gupta et al., Proceedings of the Sixth Annual Symposium on Combinatorial Pattern Matching, 1995; Kececioglu et al., http://www.techfak.uni-bielefeld. de/bcd/Lectures/kececioglu.html, 1995). In all cases, ComAlign was able to produce a solution with a score comparable to the solution obtained by MSA. The results also show that ComAlign actually does combine parts from different alignments and not just select the best of them. AVAILABILITY: The C source code (a Smalltalk version is being worked on) of ComAlign and the other programs that have been implemented in this context are free and available on WWW (http://www.daimi.au.dk/ √µcaprani). CONTACT: klaus@bucka-lassen.dk; jotun@pop.bio.au.dk;ocaprani@daimi.au.dk
An exact solution for the segment-to-segment multiple sequence alignment problem.
Authors: Lenhof H P , Morgenstern B , Reinert K
Published: July 2002

MOTIVATION: In molecular biology, sequence alignment is a crucial tool in studying the structure and function of molecules, as well as the evolution of species. In the segment-to-segment variation of the multiple alignment problem, the input can be seen as a set of non-gapped segment pairs (diagonals). Given a weight function that assigns a weight score to every possible diagonal, the goal is to choose a consistent set of diagonals of maximum weight. We show that the segment-to-segment multiple alignment problem is equivalent to a novel formulation of the Maximum Trace problem: the Generalized Maximum Trace (GMT) problem. Solving this problem to optimality, therefore, may improve upon the previous greedy strategies that are used for solving the segment-to-segment multiple sequence alignment problem. We show that the GMT can be stated in terms of an integer linear program and then solve the integer linear program using methods from polyhedral combinatorics. This leads to a branch-and-cut algorithm for segment-to-segment multiple sequence alignment. RESULTS: We report on our first computational experiences with this novel method and show that the program is able to find optimal solutions for real-world test examples.
Sequence search algorithm assessment and testing toolkit (SAT)
Authors: Park Jong , Holm Liisa , Chothia Cyrus
Published: July 2002

Motivation: The Sequence Search Algorithm Assessment and Testing Toolkit (SAT) aims to be a complete package for the comparison of different protein homology search algorithms. The structural classification of proteins can provide us with a clear criterion for judgment in homology detection. There have been several assessments based on structural sequences with classifications but a good deal of similar work is now being repeated with locally developed procedures and programs. The SAT will provide developers with a complete package which will save time and produce more comparable performance assessments for search algorithms. The package is complete in the sense that it provides a non-redundant large sequence resource database, a well-characterized query database of proteins domains, all the parsers and some previous results from PSI-BLAST and a hidden markov model algorithm.

Results: An analysis on two different data sets was carried out using the SAT package. It compared the performance of a full protein sequence database (RSDB100) with a non-redundant representative sequence database derived from it (RSDB50). The performance measurement indicated that the full database is sub-optimal for a homology search. This result justifies the use of much smaller and faster RSDB50 than RSDB100 for the SAT.

Availability: A web site is up. The whole package is accessible via www and ftp. ftp://ftp.ebi.ac.uk/pub/contrib/jong/SAThttp://cyrah.ebi.ac.uk:1111/Proj/Bio/SAThttp://www.mrc-lmb.cam.ac.uk/genomes/SATIn the package, some previous assessment results produced by the package can also be found for reference.

Contact: jong@ebi.ac.uk
MEG (Model Extender for Gepasi): a program for the

modelling of complex, heterogeneous, cellular systems
Authors: Mendes Pedro , Kell Douglas B.
Published: July 2002

Summary: We describe a program for the construction of spatially distributed metabolic models, which may then be simulated using the metabolic simulator Gepasi. This is useful for the modelling of heterogeneous systems whether as liquid cultures or as spatially organised systems with specified interconnections.

Availability: MEG runs under Windows 95, 98, 2000 and NT, with either Intel or Alpha processors, and is available from http://gepasi.dbs.aber.ac.uk/softw/meg.html

Contact: mendes@vt.edu

* To whom correspondence should be addressed. Present address: Virginia Bioinformatics Institute, Virginia Polytechnic and State University, 1750 Kraft Drive, Suite 1100, Blacksburg, VA 24061, USA.
Action–based mechanisms of attention
Authors: Tipper Steven P. , Howard Louise A. , Houghton George
Published: July 2002

Actions, which have effects in the external world, must be spatiotopically represented in the brain. The brain is capable of representing space in many different forms (e.g. retinotopic–, environment–, head– or shoulder–centred), but we maintain that actions are represented in action–centred space, meaning that, at the cellular level, the direction of movement is defined by the activity of cells. In reaching, for example, object location is defined as the direction and distance between the origin of the hand and the target. Most importantly, we argue that more than one task–relevant action can be evoked at any moment in time. Therefore, highly efficient selection processes that accurately link vision and action have had to evolve. Research is reviewed which supports the notion of action–based inhibitory mechanisms that select the target from competing distractors.
Coordinating cell fate and morphogenesis inDrosophilarenal tubules
Authors: Ainsworth Claire , Wan Susan , Skaer Helen
Published: July 2002

Using the renal tubules ofDrosophilaas an example, we explore how cell specification leads to the morphogenetic movements that underlie the generation of tissue architecture. Taking two stages of development, we show first that the tubule cells are allocated by signalling between the endodermal and ectodermal compartments of the posterior gut. Activation of the Wnt pathway patterns the ectodermal anlage, resulting in the expression of tubule genes in a subset of cells and their eversion from the hindgut to form the tubule primordia. We argue that early gene expression directs these morphogenetic movements but not the complete programme of tubule differentiation. In the second example we show that the allocation of the mitogenic tip cell lineage in each tubule is required not only for the normal pattern of cell division but also for the stereotyped three–dimensional arrangement of the mature tubules. Analysis of mutants in which the tip cell lineage is misspecified reveals that both daughters of the tip cell progenitor are required for the tubules to navigate through the body cavity, so that the distal tips locate in their characteristic positions. We show that the regulator of Rac, Myoblast city, is essential for this second morphogenetic process.
The epidemiology of human immunodeficiency virus in South Africa
Authors: Williams Brian G. , Gouws Eleanor
Published: July 2002

We review the epidemiology of human immunodeficiency virus (HIV) in South Africa where the prevalence of HIV infection is among the highest in the world. The epidemic reached South Africa relatively recently but the prevalence of infection has increased rapidly and there are significant differences among provinces. Although few 15–year–old people are infected the prevalence increases rapidly with age thereafter, especially among women. The prevalence of herpes simplex virus type 2 exceeds that of HIV and curable sexually transmitted infections are common. ‘Circular migration’ may help to explain the high rates and rapid spread of HIV in the region. The incidence of tuberculosis has increased dramatically as a result of the HIV epidemic. Antiretroviral therapy for the prevention of vertical transmission has been shown to be effective in local conditions but transmission through breast–feeding remains problematical. While some epidemiological models have been developed, much more needs to be done in this regard in order to plan, coordinate and evaluate an effective response to the epidemic. We conclude by discussing some of the research that is needed and steps that could be taken to reduce the continued spread of the infection.
Metabolic pathway analysis in trypanosomes and malaria parasites
Authors: Fairlamb Alan H.
Published: July 2002

Identification of novel drug targets is required for the development of new classes of drugs to overcome drug resistance and replace less efficacious treatments. In theory, knowledge of the entire genome of a pathogen identifies every potential drug target in any given microbe. In practice, the sheer complexity and the inadequate or inaccurate annotation of genomic information makes target identification and selection somewhat more difficult. Analysis of metabolic pathways provides a useful conceptual framework for the identification of potential drug targets and also for improving our understanding of microbial responses to nutritional, chemical and other environmental stresses. A number of metabolic databases are available as tools for such analyses. The strengths and weaknesses of this approach are discussed.
Multiobjective decision theory for computational optimization in radiation therapy
Authors: Yu Yan
Published: July 2002

Machine‐guided iterative optimization in radiation oncology requires ordinal or cardinal ranking of competing treatment plans. When the clinical objectives are multifaceted and incommensurable, the ranking formalism must take into account the decision maker's tradeoff strategies in a multidimensional decision space. To capture the decision processes in treatment planning, a multiobjective decision‐theoretic scheme is formulated. Ranking among a group of candidate plans is based on a generalized distance metric. A dynamic metric weighting function is defined based on the state energy of the decision system, which is assumed to undergo thermodynamic cooling with iteration time. The decision maker is required to specify a baseline ranking of the objectives, which is taken to be the ground state of the decision system. In addition, ultimate goals and satisficing levels can be incorporated into the ranking process. This decision‐theoretic formalism was applied to idealized cases in stereotactic radiosurgery and prostatic implantation, using the genetic algorithm as the optimization engine. The optimization pathways and the outcome at limited horizons indicated that the combined scheme of decision‐theoretic steering and iterative optimization was robust and produced treatment plans consistent with the user's expectation. The effect of treatment uncertainties was simulated using imperfect objectives. The decision process was found to be noisy in the presence of random perturbation in the objectives; however, certain recurring plans could be identified as optimized baseline solutions. Overall, the present formalism provides a realistic alternative to complete utility assessment or human‐guided exploration of the efficient solution set.
Monte Carlo calculation of dose rate distributions around wires
Authors: Ballester F. , Hernández C. , Pérez‐Calatayud J. , Lliso F.
Published: July 2002

Monte Carlo calculations of absolute dose rate in liquid water are presented in the form of away‐along tables for 1 and wires of 0.3 mm diameter. Simulated absolute dose rate values can be used as benchmark data to verify the calculation results of treatment planning systems or directly as input data for treatment planning. Best fit value of attenuation coefficient suitable for use in Sievert‐integrals‐type calculations has been derived based on Monte Carlo calculation results. For the treatment planning systems that are based on TG43 formalism we have also calculated the required dosimetry parameters.
Acoustic streaming in closed thermoacoustic devices
Authors: Bailliet Hélène , Gusev Vitalyi , Raspet Richard , Hiller Robert A.
Published: July 2002

A derivation of acoustic streaming in a steady-state thermoacoustic device is presented in the case of zero second-order time-averaged mass flux across the resonator section (nonlooped device). This yields analytical expressions for the time-independent second-order velocity, pressure gradient, and time-averaged mass flux in a fluid supporting a temperature gradient and confined between widely to closely separated solid boundaries, both in the parallel plate and in the cylindrical tube geometries (two-dimensional problem). From this, streaming can be evaluated in a thermoacoustic stack, regenerator, pulse tube, main resonator of a thermoacoustic device, or in any closed tube that supports a mean temperature gradient, providing only that the acoustic pressure, the longitudinal derivative of the pressure, and the mean temperature variation are known.
Integrality in the perception of tongue root position and voice quality in vowels
Authors: Kingston John , Macmillan Neil A. , Dickey Laura Walsh , Thorburn Rachel , Bartels Christine
Published: July 2002

In English and a large number of African and Southeast Asian languages, voice quality along a tense–lax dimension covaries with advancement of the tongue root in vowels: a laxer voice quality co-occurs with a more advanced tongue root. As laxing the voice increases energy in the first harmonic relative to higher ones and advancing the tongue root lowers F1, the acoustic consequences of these two articulations may integrate perceptually into a higher-level perceptual property, here called spectral “flatness.” Two Garner-paradigm experiments evaluated this interaction across nearly the entire range of tense–lax voice qualities and a narrow range of F1 values. The acoustic consequences of laxness and advanced tongue root integrated into spectral flatness for tenser and laxer but not for intermediate voice qualities. Detection-theoretic models developed in earlier work proved highly successful in representing the perceptual interaction between these dimensions.
The effects of varying signal intensity on the perceptual organization of rhythmic auditory patterns
Authors: Zimba Lynn D. , Robin Donald A.
Published: July 2002

Cyclic repetitions of temporally structured sequences of sound bursts and gaps are perceived as rhythmic patterns. Some are perceptually unambiguous—the pattern organization is unique; others are perceptually ambiguous—the organization changes. Previous research suggests that the pattern of neuronal adaptation and recovery from adaptation associated with these stimuli determines how listeners perceptually organize the sequences. It follows that variations in the intensity of specific sound elements, which should produce specific changes in the underlying patterns of neuronal activation, should produce predictable changes in the perceptual organization of the sequences. The present study tested this hypothesis by observing the perceptual responses of listeners while varying the intensity of critical elements of unambiguous and ambiguous sequences. The results support the hypothesis in that an unambiguous sequence was made ambiguous and an ambiguous sequence was made less ambiguous. However, the unambiguous sequence did not completely reverse its perceptual organization, nor did the ambiguous sequence become completely unambiguous. The outcome is discussed focusing on the range of intensity increments tested, the type of stimuli used, and the possibility that neurosensory factors may interact with other organizing factors in determining the perceptual organization of rhythmic auditory sequences.
Ripple depth and density resolution of rippled noise
Authors: Supin A. Ya. , Popov V. V. , Milekhina O. N. , Tarakanov M. B.
Published: July 2002

Depth resolution of spectral ripples was measured in normal humans using a phase-reversal test. The principle of the test was to find the lowest ripple depth at which an interchange of peak and trough position (the phase reversal) in the rippled spectrum is detectable. Using this test, ripple-depth thresholds were measured as a function of ripple density of octave-band rippled noise at center frequencies from 0.5 to 8 kHz. The ripple-depth threshold in the power domain was around 0.2 at low ripple densities of 4–5 relative units (center-frequency-to-ripple-spacing ratio) or 3–3.5 ripples/oct. The threshold increased with the ripple density increase. It reached the highest possible level of 1.0 at ripple density from 7.5 relative units at 0.5 kHz center frequency to 14.3 relative units at 8 kHz (5.2 to 10.0 ripple/oct, respectively). The interrelation between the ripple depth threshold and ripple density can be satisfactorily described by transfer of the signal by frequency-tuned auditory filters.
Complex tone processing in primary auditory cortex of the awake monkey. I. Neural ensemble correlates of roughness
Authors: Fishman Yonatan I. , Reser David H. , Arezzo Joseph C. , Steinschneider Mitchell
Published: July 2002

Previous physiological studies [e.g., Bieser and Muller-Preuss, Exp. Brain Res. 108, 273–284 (1996); Schulze and Langner, J. Comp. Physiol. A 181, 651–663 (1997); Steinschneider et al., J. Acoust. Soc. Am. 104, 2935–2955 (1998)] have suggested that neural activity in primary auditory cortex (A1) phase-locked to the waveform envelope of complex sounds with low (<300 Hz) periodicities may represent a neural correlate of roughness perception. However, a correspondence between these temporal response patterns and human psychophysical boundaries of roughness has not yet been demonstrated. The present study examined whether the degree of synchronized phase-locked activity of neuronal ensembles in A1 of the awake monkey evoked by complex tones parallels human psychoacoustic data defining the existence region and frequency dependence of roughness. Stimuli consisted of three consecutive harmonics of fundamental frequencies (f0s) ranging from 25 to 4000 Hz. The center frequency of the complex tones was fixed at the best frequency (BF) of the cortical sites, which ranged from 0.3 to 10 kHz. Neural ensemble activity in the thalamorecipient zone (lower lamina III) and supragranular cortical laminae (upper lamina III and lamina II) was measured using multiunit activity and current source density techniques and the degree of phase-locking to the f0 was quantified by spectral analysis. In the thalamorecipient zone, the stimulus f0 at which phase-locking was maximal increased with BF and reached an upper limit between 75 and 150 Hz for BFs greater than about 3 kHz. Estimates of limiting phase-locking rates also increased with BF and approximated psychoacoustic values for the disappearance of roughness. These physiological relationships parallel human perceptual data and therefore support the relevance of phase-locked activity of neuronal ensembles in A1 for the physiological representation of roughness.
Distributed cooperative fault detection and isolation for uncertain multi‐agent systems based on zonotope theory
Authors: Zhang Xiangming , Zhu Fanglai
Published: March 2022

In recent years, multi‐agent system (MAS) have attracted extensive attention, but the study for MAS via zonotope theory is very few. This article considers the distributed cooperative fault detection (FD) and fault isolation (FI) problems for a MAS, in which every agent is assumed to be with disturbances in both the sate equation and output equation, by combining Luenberger‐like observers and zonotope theory. To begin with, a robust observer is constructed for each agent, and zonotope theory is applied on the error dynamic system of the observer such that the boundary estimation of the system state can be computed iteratively when the MAS has no fault. After this, for distributed cooperative FD purpose, a residual is also constructed based on the observer. Because the constructed residual contains disturbance, it cannot be used for FD directly. To overcome this drawback, the interval estimation of the residual is calculated by using zonotope method, and based on the residual interval estimate, a residual‐based distributed cooperative FD strategy is presented. Moreover, the distributed cooperative FI scheme is discussed and an FI strategy is also developed by modifying the distributed cooperative FD scheme. Finally, a simulation example is presented to show the effectiveness and advantages of the proposed method.
A Novel Electrochemiluminescence Janus Emitter for Dual‐Mode Biosensing
Authors: Han Tingting , Ma Cheng , Wang Leyong , Cao Yue , Chen Hong‐Yuan , Zhu Jun‐Jie
Published: March 2022

A novel electrochemiluminescence (ECL) Janus emitter realizes dual‐mode biosensing for multiple disease‐related biomarkers from cells. Each Janus emitter consists of ruthenium (II) complex and luminol polymer doped hemispheres that are spatially separated but function simultaneously, generating intense dual‐ECL emissions. This design effectively eliminates optical and electrochemical interferences between different ECL mono‐luminophores in comparison with the homogenous nanostructures, thereby improving ECL efficiency and detection sensitivity. Accordingly, the ECL Janus emitters provide a proof of concept for the construction of the ratiometric ECL sensing of H2O2. Furthermore, this Janus emitter enables simultaneous identification and quantification of the intracellular cancer‐related dual microRNAs. This work not only inspires the development of ECL Janus emitters, but also highlights their potential in bioanalysis and clinical diagnosis in the future.
Interfacial Ion‐Trapping Electrolyte‐Gated Transistors for High‐Fidelity Neuromorphic Computing
Authors: Jin Minho , Lee Haeyeon , Im Changik , Na Hyun‐Jae , Lee Jae Hak , Lee Won Hyung , Han Junghyup , Lee Eungkyu , Park Junwoo , Kim Youn Sang
Published: March 2022

Li+ electrolyte‐gated transistors (EGTs) have received much attention as artificial synapses for neuromorphic computing. EGTs, however, have been still challenging to achieve long‐term synaptic plasticity, which should be linearly and symmetrically controlled with the magnitude of electrical potential at the gate electrode. Herein, a fluoroalkylsilane (FAS) self‐assembled monolayer (SAM) is introduced as a channel‐electrolyte interlayer with the function of sequential ion‐trapping in Li+ EGTs. It is demonstrated that the retention of Li+ ions can be enhanced, resulting in stable non‐volatile channel conductance update with high fidelity, linearity, and symmetry in EGTs treated with FAS with 5 fluoroalkyl chains. Through investigating electrical analysis and chemical analysis, it is verified that fluoroalkyl chains enable the sequential ion‐trapping at the channel‐electrolyte interface by coulombic attraction between Li+ ions and fluorocarbons. Simulations of artificial neural networks using 20 × 20 digits show FAS‐treated EGTs are suitable as artificial synapses with an accuracy of 89.71% by identical gate pulses and 91.97% by non‐identical gate pulses. A methodological approach is newly introduced for developing synaptic devices based on EGTs for neuromorphic computing with high fidelity.
Robust Lithium–Sulfur Batteries Enabled by Highly Conductive WSe2‐Based Superlattices with Tunable Interlayer Space
Authors: Zhang Chaoqi , Fei Ban , Yang Dawei , Zhan Hongbing , Wang Jiaao , Diao Jiefeng , Li Junshan , Henkelman Graeme , Cai Daoping , Biendicho Jordi Jacas , Morante Joan Ramon , Cabot Andreu
Published: March 2022

Superlattices are rising stars on the horizon of energy storage and conversion, bringing new functionalities; however, their complex synthesis limits their large‐scale production and application. Herein, a simple solution‐based method is reported to produce organic–inorganic superlattices and demonstrate that the pyrolysis of the organic compound enables tuning their interlayer space. This strategy is exemplified here by combining polyvinyl pyrrolidone (PVP) with WSe2within PVP/WSe2superlattices. The annealing of such heterostructures results in N‐doped graphene/WSe2(NG/WSe2) superlattices with a continuously adjustable interlayer space in the range from 10.4 to 21 Å. Such NG/WSe2superlattices show a metallic electronic character with outstanding electrical conductivities. Both experimental results and theoretical calculations further demonstrate that these superlattices are excellent sulfur hosts at the cathode of lithium–sulfur batteries (LSB), being able to effectively reduce the lithium polysulfide shuttle effect by dual‐adsorption sites and accelerating the sluggish Li–S reaction kinetics. Consequently, S@NG/WSe2electrodes enable LSBs characterized by high sulfur usages, superior rate performance, and outstanding cycling stability, even at high sulfur loadings, lean electrolyte conditions, and at the pouch cell level. Overall, this work not only establishes a cost‐effective strategy to produce artificial superlattice materials but also pioneers their application in the field of LSBs.
MXene‐Enhanced Chitin Composite Sponges with Antibacterial and Hemostatic Activity for Wound Healing
Authors: Li Shanshan , Gu Bin , Li Xiaoyun , Tang Shuwei , Zheng Lu , Ruiz‐Hitzky Eduardo , Sun Zeyu , Xu Changliang , Wang Xiaoying
Published: March 2022

This study shows the effective use of MXene‐based nanomaterials to improve the performance of biocomposite sponges in wound healing. In this way, diverse chitin/MXene composite sponges are fabricated by incorporating MXene‐based nanomaterials with various morphology (accordion‐shaped, intercalated, single‐layer, gold nanoparticles (AuNPs)‐loaded single‐layer) into the network of chitin sponge (CH), which can prevent massive blood losses and promote the healing process of bacterial‐infected wounds. With the addition of MXene‐based nanomaterials, the hemostatic efficacy of CH is enhanced due to the improved hemophilicity and accelerated blood coagulation kinetics. Furthermore, the composite sponges show a predominant antibacterial activity through the synergy between the capture and the photothermal effects. Importantly, the addition of AuNPs to composite sponges further improves hemostatic performance and promotes normal skin cell migration to heal the infected wound, achieving wound closure rates of 84% on day 9. These initial studies expand the applications of MXene‐based nanomaterials in biomedical fields.
Vascularized Lung Cancer Model for Evaluating the Promoted Transport of Anticancer Drugs and Immune Cells in an Engineered Tumor Microenvironment
Authors: Kim Dasom , Hwang Kyeong Seob , Seo Eun U , Seo Suyeong , Lee Byung Chul , Choi Nakwon , Choi Jonghoon , Kim Hong Nam
Published: March 2022

The tumor microenvironment (TME) is the environment around the tumor, including blood vessels, immune cells, fibroblasts, signaling molecules, and the extracellular matrix (ECM). Owing to its component interactions, the TME influences tumor growth and drug delivery in a highly complex manner. Although several vascularized cancer models are developed to mimic the TME in vitro, these models cannot comprehensively reflect blood vessel–tumor spheroid interactions. Here, a method for inducing controlled tumor angiogenesis by engineering the microenvironment is presented. The interstitial flow direction regulates the direction of capillary sprouting, showing that angiogenesis occurs in the opposite direction of flow, while the existence of lung fibroblasts affects the continuity and lumen formation of sprouted capillaries. The vascularized tumor model shows enhanced delivery of anticancer drugs and immune cells to the tumor spheroids because of the perfusable vascular networks. The possibility of capillary embolism using anticancer drug‐conjugated liquid metal nanoparticles is investigated using the vascularized tumor model. This vascularized tumor platform can aid in the development of effective anticancer drugs and cancer immunotherapy.
Ultrahigh‐Speed In‐Memory Electronics Enabled by Proximity‐Oxidation‐Evolved Metal Oxide Redox Transistors
Authors: Kumar Mohit , Kim Unjeong , Lee WangGon , Seo Hyungtak
Published: March 2022

The pursuit of a universal device that combines nonvolatile multilevel storage, ultrafast writing/erasing speed, nondestructive readout, and embedded processing with low power consumption demands the development of innovative architectures. Although thin‐film transistors and redox‐based resistive‐switching devices have independently been proven to be ideal building blocks for data processing and storage, it is still difficult to achieve both well‐controlled multilevel memory and high‐precision ultrafast processing in a single unit, even though this is essential for the large‐scale hardware implementation of in‐memory computing. In this work, an ultrafast (≈42 ns) and programable redox thin‐film transistor (ReTFT) memory made of a proximity‐oxidation‐grown TiO2 layer is developed, which has on/off ratio of 105, nonvolatile multilevel analog storage with a long retention time, strong durability, and high reliability. Utilizing the proof‐of‐concept ReTFTs, circuits capable of performing fundamental NOT, AND, and OR operations with reconfigurable logic‐in‐memory processing are developed. Further, on‐demand signal memory‐processing operations, like multi‐terminal addressable memory, learning, pattern recognition, and classification, are explored for prospective application in neuromorphic hardware. This device, which operates on a fundamentally different mechanism, presents an alternate solution to the problems associated with the creation of high‐performing in‐memory processing technology.
Emerging Biosensing Technologies for the Diagnostics of Viral Infectious Diseases
Authors: Kabay Gözde , DeCastro Jonalyn , Altay Alara , Smith Kasey , Lu Hsiang‐Wei , Capossela Antonia McDonnell , Moarefian Maryam , Aran Kiana , Dincer Can
Published: March 2022

Several viral infectious diseases appear limitless since the beginning of the 21st century, expanding into pandemic lengths. Thus, there are extensive efforts to provide more efficient means of diagnosis, a better understanding of acquired immunity, and improved monitoring of inflammatory biomarkers, as these are all crucial for controlling the spread of infection while aiding in vaccine development and improving patient outcomes. In this regard, various biosensors have been developed recently to streamline pathogen and immune response detection by addressing the limitations of traditional methods, including isothermal amplification‐based systems and lateral flow assays. This review explores state‐of‐the‐art biosensors for detecting viral pathogens, serological assays, and inflammatory biomarkers from the material perspective, by discussing their advantages, limitations, and further potential regarding their analytical performance, clinical utility, and point‐of‐care adaptability. Additionally, next‐generation biosensing technologies that offer better sensitivity and selectivity, and easy handling for end‐users are highlighted. An emerging example of these next‐generation biosensors are those powered by novel synthetic biology tools, such as clustered regularly interspaced short palindromic repeats (CRISPR) with CRISPR‐associated proteins (Cas), in combination with integrated point‐of‐care devices. Lastly, the current challenges are discussed and a roadmap for furthering these advanced biosensing technologies to manage future pandemics is provided.
An Open‐Ended Ni3S2–Co9S8 Heterostructures Nanocage Anode with Enhanced Reaction Kinetics for Superior Potassium‐Ion Batteries
Authors: Zhang Shipeng , Ling Fangxin , Wang Lifeng , Xu Rui , Ma Mingze , Cheng Xiaolong , Bai Ruilin , Shao Yu , Huang Huijuan , Li Dongjun , Jiang Yu , Rui Xianhong , Bai Jintao , Yao Yu , Yu Yan
Published: March 2022

Sulfides are perceived as promising anode materials for potassium‐ion batteries (PIBs) due to their high theoretical specific capacity and structural diversity. Nonetheless, the poor structural stability and sluggish kinetics of sulfides lead to unsatisfactory electrochemical performance. Herein, Ni3S2–Co9S8 heterostructures with an open‐ended nanocage structure wrapped by reduced graphene oxide (Ni‐Co‐S@rGO cages) are well designed as the anode for PIBs via a selective etching and one‐step sulfuration approach. The hollow Ni‐Co‐S@rGO nanocages, with large surface area, abundant heterointerfaces, and unique open‐ended nanocage structure, can reduce the K+ diffusion length and promote reaction kinetics. When used as the anode for PIBs, the Ni‐Co‐S@rGO exhibits high reversible capacity and low capacity degradation (0.0089% per cycle over 2000 cycles at 10 A g–1). A potassium‐ion full battery with a Ni‐Co‐S@rGO anode and Prussian blue cathode can display a superior reversible capacity of 400 mAh g–1 after 300 cycles at 2 A g–1. The unique structural advantages and electrochemical reaction mechanisms of the Ni‐Co‐S@rGO are revealed by finite‐element‐simulation in situ characterizations. The universal synthesis technology of bimetallic sulfide anodes for advanced PIBs may provide vital guidance to design high‐performance energy‐storage materials.
Microneedle‐Based Technology: Toward Minimally Invasive Disease Diagnostics
Authors: Xu Na , Xu Wenxin , Zhang Manyue , Yu Jia , Ling Guixia , Zhang Peng
Published: March 2022

The traditional way of disease diagnosis is to detect biomarkers in serum, blood, urine, and saliva, but it often faces wound infection and pain, and usually requires professional medical personnel to operate, which is unacceptable for most people. As a result, minimally invasive detection of biomarkers has attracted wide attention and is expected to become a new method for patient monitoring and disease diagnosis. Interstitial fluid (ISF) acts as a medium between cells and the circulatory system, serving as a reservoir of biomolecules, nutrients, and metabolic products. Microneedles (MNs) are effective carriers for delivering drugs, biomolecules, vaccines, and stem cells. What's more, MNs provide a painless, simple, and minimally invasive method to collect skin ISF. In summary, the structural and functional characteristics of MNs provide incomparable advantages and open the door for future diagnosis and monitoring. MNs techniques are minimally invasive, convenient, and patient compliant for individualized and long‐term treatments, which open up new areas of disease diagnosis. In this review, various MNs techniques for ISF sampling in disease diagnosis are reviewed, and their future challenges and development prospects are discussed.