bluuebunny/crossref_metadata_2025 huggingface dataset:
Kalman Filter Implementation of Self-Organizing Feature Maps
Authors: Haese Karin
Published: July 2002

The self-organizing learning algorithm of Kohonen and most of its extensions are controlled by two learning parameters, the learning coefficient and the width of the neighborhood function, which have to be chosen empirically because neither rules nor methods for their calculation exist. Consequently, often time-consuming parameter studies precede neighborhood-preserving feature maps of the learning data. To circumvent those lengthy numerical studies, this article describes the learning process by a state-space model in order to use the linear Kalman filter algorithm training the feature maps. Then the Kalman filter equations calculate the learning coefficient online during the training, while the width of the neighborhood function needs to be estimated by a second extended Kalman filter for the process of neighborhood preservation.

The performance of the Kalman filter implementation is demonstrated on toy problems as well as on a crab classification problem. The results of crab classification are compared to those of generative topographic mapping, an alternative method to the self-organizing feature map.
Sahmatah: Awakening History
Authors: Mast Edward
Published: July 2002

From memories of the ruins of an Arab village destroyed by the Israeli army, a Palestinian theatre piece emerges.
ÜBER DIE URSACHEN DES SIEGES DES CHRISTENTUMS IN ÄGYPTEN
Authors: Hubai Peter
Published: July 2002

One hundred and eighty years of egyptological scholarship has failed to establish why and how the ancient Egyptian religion could be surmounted by Christianity. In recent decades scholars have attributed Christianity's triumph to Christian revelation, the moral superiority of Christianity, its more thoroughly social sensibility, monotheism, its domination over the heimarmene, etc. The riddle is intensified if we consider that by the time of the decay of the autochthonous Egyptian religion in the home country, the so-called Isis religion was victorious in other provinces of the Imperium Romanum. The present paper argues that the two religions represent two different types, the Egyptian one being an ethnic religion, Christianity being a universal one. Consequently, the Egyptian religion had no need of soteria, while Christianity was born in a situation of "Unheil". During the last millennium of the pharaonic history the crisis of the traditional religion became more and more serious, because the cleft between cult and the native culture supporting this cult became too deep. This conclusion is supported by the decline of the hieroglyphic and demotic scripture, the disappearing of the characteristic Egyptian art and the profound change in the anthropological understanding of human being, which might have required the soteriology of a new religion.
"ABER GOTT WIRD MEINE SEELE ERLÖSEN" – TOD UND LEBEN NACH PSALM XLIX
Authors: Witte Markus
Published: July 2002

Ps XLIX bildet, abzüglich der Überschrift und der Glossen in V 9 und V 15* (), eine literarisch einheitliche Meditation über das allgemeine Todesgeschick. Die des Sterbens aller Menschen kontrastiert der Psalmist mit der Hoffnung auf postmortale Auslösung seiner Seele () aus der Scheol. In V 15-6 deutet sich die von der Unsterblichkeit der Seele als eines von der äußeren Gestalt () Menschen zu unterscheidenden, dabei dessen Identität wahrenden Aspekts an. für die Theologie des Psalms ist die Verbindung von Glaube und Einsichtig zu sein () bedeutet, zwischen Leben und Tod bzw. Gottesmacht Menschenmacht differenzieren zu können und angesichts der Rätselhaftigkeit der auf den den Tod überwindenden Gott zu vertrauen. Literatur- und religionsgeschichtlich gehört der Psalm aufgrund seiner Parallelen zu Kohelet und zu Äthhen xcviii wohl in die zweite Hälfte des 3. Jh. v. Chr.
THE SIGNIFICANCE OF THE 'HAND ON THE MOUTH' GESTURE IN JOB XL 4
Authors: Glazov Gregory Yuri
Published: July 2002

Contrary to the prevailing assumption that the Book of Job concludes with Job 'putting his hand on his mouth', a better understanding of the meanings of this gesture and of its relation to the rhetoric of the Book of Job, provides a vital clue towards a better understanding of the purpose of the second divine speech and the meaning of the Book of Job.
LATERAL PLATE VARIATION IN GALICIAN STICKLEBACK POPULATIONS IN THE RIVERS MIÑO AND LIMIA, NW SPAIN
Authors: Fernández  , Hermida  , Amaro  , Miguel E. San
Published: July 2002

We examined lateral plate variation in populations of stickleback, Gasterosteus aculeatus, from the rivers Miño and Limia in Galicia (Northwest Spain), by analysing morphs, number of lateral plates, and position of the plates. In order to test for sexual dimorphism, the means and variances of plates were compared in males and females of some populations. No significant differences were found between sexes, therefore all remaining populations were analysed without controlling for sex. As stickleback populations in Galicia have an annual life span, the populations from the river Miño were divided in two age groups to compare lateral plate number. Analysis of each group revealed significant differences among populations, in accordance with the large amount of variation found in populations from other regions. Analysis of samples collected from the same place and at the same time of year, but in different years, indicated that there was little year to year variation. This suggests that populations are well adapted to their habitat, or that environmental conditions did not change significantly during the period of sampling. Finally, we propose a new method for the evaluation of scute variation analysis of the position of lateral plates. Cluster analysis of our data clearly differentiated populations from the rivers Miño and Limia.
ON THE PHYLOGENY OF LAKE BAIKAL AMPHIPODS IN THE LIGHT OF MITOCHONDRIAL AND NUCLEAR DNA SEQUENCE DATA
Authors: Kamaltynov  , Vainola  , Ogarkov  , Vainio  , Verheyen  , Sherbakov D. Yu.
Published: July 2002

Two DNA sequence data sets, one from the nuclear 18S rRNA gene (520 bp long), the other from the mitochondrial COI gene (540 bp), are used to characterize the evolutionary history of the endemic Baikalian amphipod species assemblage. The observed differentiation suggests that the initial radiation of Baikalian lineages was ancient, probably older than the emergence of the initial large paleolake within the current lake basin in the mid-Tertiary. The mtDNA data suggest a principal division between the smooth fossorial genus Micruropus and the remaining Baikalian amphipod taxa included in the study. The monophyly of the Baikalian taxa with respect to the non-Baikalian Gammarus cannot be conclusively inferred from the mitochondrial sequences. The 18S rRNA data, however, suggest that the pelagic Baikalian species Macrohectopus branickii is closer to the European Gammarus pulex than to any other gammarid studied, and give an indication of a polyphyletic origin of the Baikalian amphipod fauna. Also, within the Baikalian assemblage, the major genera with strongly developed body armature, Acanthogammarus and Pallasea, may be polyphyletic. Deux ensembles de donnees de sequences du DNA, l'un concernant le 18S rRNA nucleaire (520 pb), l'autre le gene mitochondrial COI (540 pb) sont utilises pour caracteriser l'histoire evolutive de l'assemblage des especes d'amphipodes endemiques du Baikal. La differenciation observee suggere que la radiation initiale des lignees baikaliennes est ancienne, probablement plus ancienne que l'emergence du grand paleolac initial a l'interieur du bassin lacustre du tertiaire moyen. Les donnees du mtDNA suggerent une division principale entre le genre fouisseur lisse Micruropus et les taxa baikaliens restants, inclus dans l'etude. La monophylie des taxons baikaliens par rapport aux Gammarus non baikaliens ne peut pas etre deduite de facon concluante des sequences mitochondriales. Les donnees du 18S rRNA, cependant, suggerent que l'espece pelagique baikalienne Macrohectopus branickii est plus proche du Gammarus pulex europeen que de n'importe quel autre gammaride etudie, et donnent une indication de l'origine polyphyletique de la faune baikalienne d'amphipodes. De meme, dans l'assemblage baikalien, les genres majeurs aavec une armature du corps fortement developpee, Acanthogammarus et Pallasea , pourraient etre ppolyphyletiques.
The application of safranin-O for staining virus-vector trichodorid nematodes for electron and confocal laser scanning microscopy
Authors: Karanastasi Eirini , Vellios Evangelos , Roberts Ian , MacFarlane Stuart , Brown Derek J.F.
Published: July 2002

Post-fixation with osmium tetroxide (OsO4), prior to examination by electron
microscopy, enables nematodes to be located in epoxy-resin blocks, and
improves contrast of ultrastructural features. For specimen visibility,
alternatives to OsO4 were examined as it can inhibit antigenicity, thus
preventing application of serological techniques. Basic fuchsin stain does
not affect antigenicity and when applied to trichodorids enabled specimens
to be readily located in the block, but had several disadvantages such as
causing substantial alteration of the nematode structure. Safranin-O stain
enabled Paratrichodorus anemones and P. pachydermus specimens to be located
in resin blocks, different parts of the nematode body to be distinguished,
and did not affect specimen ultrastructure. Also, with viruliferous
specimens it allowed immunogold labelling techniques to be applied for
identifying tobacco rattle virus particles at the site of retention in the
nematodes. Safranin-O is fluorescent and this feature was used to examine
sections from the spicula region of a male P. pachydermus specimen under a
confocal laser scanning microscope. La post-fixation au tétroxyde d’osmium
(OsO4) avant l’observation en microscopie électronique empêche la
localisation des nématodes dans les blocs de résine epoxy et augmente le
contraste des caractéristiques ultrastructurales. Pour la localisation des
spécimens, des solutions alternatives au OsO4, qui peut inhiber
l’antigénicité et donc empêcher l’application de techniques sérologiques,
ont été examinées. Le coloration à la fuschine basique n’affecte pas
l’antigénicité et permet de situer les spécimens dans les blocs, mais elle
présente de nombreux désavantages telle l’altération substantielle des
structures du nématode. La safranine-O permet la localisation de
Paratrichodorus anemones et de P. pachydermus, les différentes parties du
corps du nématode étant alors identifiables, et n’affecte en rien
l’ultrastructure du nématode. Chez les spécimens portant des virus, elle
permet également l’utilisation de techniques de marquage immunologique à
l’or pour identifier les particules du virus du tobacco rattle dans les
sites de rétention chez le nématode. La safranine-O est fluorescente et
cette particularité a été utilisée pour observer des sections de la région
des spicules chez un mâle de P. pachydermus en microscopie confocale à
balayage.
SXP/RAL-2 proteins of the potato cyst nematode Globodera rostochiensis: secreted proteins of the hypodermis and amphids
Authors: Jones John , Blok Vivian , Smant Geert
Published: July 2002

A family of secreted proteins (the SXP/RAL-2 proteins) has been identified in animal parasitic nematodes and Caenorhabditis elegans. In this paper, we describe two full length cDNA sequences from the potato cyst nematode Globodera rostochiensis which could encode proteins similar to SXP/ RAL-2 proteins. We show that although both genes are expressed in second stage juveniles and in sedentary females of G. rostochiensis, they have remarkably different spatial expression patterns. The mRNA derived from one of the genes (gr-sxp-1) was present in the hypodermis, as has been described previously for one of these genes in an animal parasitic nematode. However, expression of the mRNA from the other gene was restricted to the gland cells surrounding the amphidial sense organs (the sheath cells). In addition to providing the first description of SXP proteins from a plant parasitic nematode, this work provides the first detailed characterisation of a protein secreted from the amphids of a plant parasite. Les protéines SXP/ RAL-2 du nématode à kyste de la pomme de terre Globodera rostochiensis : les protéines sécrétées par l'hypoderme et les amphides - Une famille de protéines sécrétées - les protéines SXP/RAL-2 - avait déjà été identifiée chez les nématodes zooparasites et chez Caenorhabditis elegans. Dans cet article nous décrivons deux séquences en longueur totale de cADN provenant du nématode à kyste de la pomme de terre Globodera rostochiensis, séquences qui pourraient coder des protéines similaires aux protéines SXP/RAL-2. Nous montrons que, bien que l'un et l'autre gène s'expriment chez les juvéniles de deuxième stade et chez les femelles sédentaires de Globodera rostochiensis, ils possèdent des profils d'expression spatiale remarquablement différents. Le rARN dérivé à partir d'un de ces gènes (gr-sxp-1) était présent dants l'hypoderme, comme cela avait déjà été décrit pour l'un de ces gènes chez un nématode zooparasite. Cependant, l'expression du mRNA de l'autre gène était limitée aux cellules glandulaires entourant les organes sensoriels amphidiens (les cellules de la gaine). Offrant la première description de protéines SXP provenant de nématodes phytopathogènes, le présent travail fournit de plus la première caractérisation détaillée d'une protéine sécrétée par les amphides d'un nématode parasite de plantes.
history studies of the hermaphrodite nematode Acrobeloides sp. with Pseudomonas cepacia as a food source on agar
Authors: Ikonen Eeva
Published: July 2002

The life cycle and reproduction of a species of Acrobeloides isolated from native North American prairie soil was studied in monoxenic cultures with Pseudomonas cepacia as a food source at 23°C. The demographic parameters were calculated from cultures for the period from 0 to 15 days. The intrinsic rate of natural increase (rm) was 0.38 days, mean total productivity of Acrobeloides sp. without predation (R0) in 15 days was 87.7, and capacity of increase (rc) was 0.36. The minimum generation time (Tmin) was 10 days, cohort generation time (Tc) 6.8 days and mean generation time (T) 18.5 days. The age of an adult female at median egg laying (T) was 7.9 days, and mortality (lx) 0.4. The estimation of consumption of Acrobeloides sp. by nematophagous mites, expressed in organic carbon content, was 0.22 μg day-1. Based on laboratory experiments, this Acrobeloides sp. from native prairie soil does not have a high ability for population growth with Pseudomonas cepacia as food source at 23°C.
Pastors and Priests in the Early Modern Grisons: Organized Profession or Side Activity
Authors: Pfister Ulrich
Published: July 2002

Duringthe era of church reforms the clergy tended to become a profession—at least such has been argued with respect to English ministers during the sixteenth and seventeenth centuries.1The present study endeavors to show that an analysis of the shifting position of the clergy in the continuum between a nonagricultural side activity, an estate in traditional society, and a profession can contribute to our understanding of the role that clergymen played in early modern church reforms, confessionalization, social discipline, and acculturation.
Manganoan berthierine, Meyers Pass, New Zealand: occurrence in the prehnite-pumpellyite facies
Authors: Coombs D. S. , Zhao G. , Peacor D. R.
Published: July 2002

Manganoan berthierine, sometimes only a few layers thick, is preserved interlayered with manganoan chlorite (chamosite) in small recrystallized patches in cherty metapelagites matamorphosed in the prehnite–pumpellyite facies at Meyers Pass, Torlesse Terrane, South Canterbury, New Zealand. The Mn occupies 11–12% of the octahedral sites, making this the most Mn–rich berthierine reported so far. The ratio (Fe+Mn)(Fe+Mn+Mg), 0.67–0.70, is at the lower end of those of previously reported occurrences, making these amongst the most Mg-rich berthierines known. Manganoan berthierine and interlayered manganoan chlorite also make up ~11–13% of the cryptocrystalline groundmass in which the berthierine is believed to have crystallized under early diagenetic conditions near a deep-ocean–sediment interface. The occurrence of berthierine in the recrystallized patches lends support to the possibility of a stability field at the temperature of prehnite-pumpellyite facies recrystallization in association with chlorite of similar but not identical composition.
Impaired dendritic cell maturation in patients with chronic, but not resolved, hepatitis C virus infection
Authors: Auffermann-Gretzinger Susanne , Keeffe Emmet B. , Levy Shoshana
Published: July 2002

Dendritic cells (DCs) are important for the initiation of immune responses to foreign antigens. Their antigen uptake and presentation capacities enable them to prime and activate T cells. Immature DCs capture antigens; however, they must be activated to mature before serving as efficient antigen-presenting cells. The antigen-presenting capacity of DCs can be diminished during viral infection and as a consequence of tumor formation. Chronic infection with hepatitis C virus (HCV) has been shown to affect the allostimulatory function of DCs. In this study, it is demonstrated that monocyte-derived DCs from patients with chronic HCV infection do not respond to maturation stimuli. Instead, they maintain their immature phenotype, reflected by the pattern of cell surface markers and by their continued capacity to uptake antigen. Moreover, their allostimulatory abilities are impaired compared with those of mature DCs derived from healthy donors. To investigate a possible correlation between viral clearance and this DC maturation defect, patients with resolved HCV infection after a course of antiviral therapy were studied. Results demonstrate that DCs from patients who cleared HCV behaved like DCs from healthy donors: in response to maturation stimuli, they decrease antigen uptake, up-regulate expression of appropriate surface markers, and are potent stimulators of allogeneic T cells.
Basis of hematopoietic defects in platelet-derived growth factor (PDGF)-B and PDGF β-receptor null mice
Authors: Kaminski Wolfgang E. , Lindahl Per , Lin Nancy L. , Broudy Virginia C. , Crosby Jeffrey R. , Hellström Mats , Swolin Birgitta , Bowen-Pope Daniel F. , Martin Paul J. , Ross Russell , Betsholtz Christer , Raines Elaine W.
Published: July 2002

Platelet-derived growth factor (PDGF)-B and PDGF β-receptor (PDGFRβ) deficiency in mice is embryonic lethal and results in cardiovascular, renal, placental, and hematologic disorders. The hematologic disorders are described, and a correlation with hepatic hypocellularity is demonstrated. To explore possible causes, the colony-forming activity of fetal liver cells in vitro was assessed, and hematopoietic chimeras were demonstrated by the transplantation of mutant fetal liver cells into lethally irradiated recipients. It was found that mutant colony formation is equivalent to that of wild-type controls. Hematopoietic chimeras reconstituted with PDGF-B−/−, PDGFRβ−/−, or wild-type fetal liver cells show complete engraftment (greater than 98%) with donor granulocytes, monocytes, B cells, and T cells and display none of the cardiovascular or hematologic abnormalities seen in mutants. In mouse embryos, PDGF-B is expressed by vascular endothelial cells and megakaryocytes. After birth, expression is seen in macrophages and neurons. This study demonstrates that hematopoietic PDGF-B or PDGFRβ expression is not required for hematopoiesis or integrity of the cardiovascular system. It is argued that metabolic stress arising from mutant defects in the placenta, heart, or blood vessels may lead to impaired liver growth and decreased production of blood cells. The chimera models in this study will serve as valuable tools to test the role of PDGF in inflammatory and immune responses.
A model of human p210bcr/ABL-mediated chronic myelogenous leukemia by transduction of primary normal human CD34+ cells with a BCR/ABL-containing retroviral vector
Authors: Zhao Robert C. , Jiang Yuehua , Verfaillie Catherine M.
Published: July 2002

Most insights into the molecular mechanisms underlying transformation by the p210BCR/ABL oncoprotein are derived from studies in which BCR/ABL cDNA was introduced into hematopoietic or fibroblast cell lines. However, such cell line models may not represent all the features of chronic myelogenous leukemia (CML) caused by additional genetic abnormalities and differences in the biology of cell lines compared with primary hematopoietic progenitor and stem cells. A primary human hematopoietic progenitor cell model for CML was developed by the transduction of b3a2 BCR/ABL cDNA in normal CD34+cells. Adhesion of BCR/ABL-transduced CD34+ cells to fibronectin was decreased, but migration over fibronectin was enhanced compared with that of mock-transduced CD34+ cells. Adhesion to fibronectin did not decrease the proliferation of BCR/ABL-transduced CD34+ cells but decreased the proliferation of mock-transduced CD34+ cells. This was associated with elevated levels of p27Kip in p210BCR/ABL-expressing CD34+ cells. In addition, the presence of p210BCR/ABLdelayed apoptosis after the withdrawal of cytokines and serum. Finally, significantly more and larger myeloid colony-forming units grew from BCR/ABL than from mock-transduced CD34+ cells. Thus, the transduction of CD34+ cells with the b3a2-BCR/ABL cDNA recreates most, if not all, phenotypic abnormalities seen in primary CML CD34+ cells. This model should prove useful for the study of molecular mechanisms associated with the presence of p210BCR/ABL in CML.
Stable remission after administration of the receptor tyrosine kinase inhibitor SU5416 in a patient with refractory acute myeloid leukemia
Authors: Mesters Rolf M. , Padró Teresa , Bieker Ralf , Steins Martin , Kreuter Michael , Göner Michael , Kelsey Stephen , Scigalla Paul , Fiedler Walter , Büchner Thomas , Berdel Wolfgang E.
Published: July 2002

The small molecule receptor tyrosine kinase (RTK) inhibitor SU5416 targets the vascular endothelial growth factor receptor 2 and the stem cell factor receptor c-kit. Herein is described the successful treatment of a 65-year-old woman with SU5416, in second relapse of acute myeloid leukemia (AML) and refractory toward standard chemotherapy regimens. After 12 weeks of treatment with SU5416, the blast cell counts (blood and bone marrow) decreased to undetectable levels and the peripheral blood cell counts normalized with the exception of the platelet count (50-80 × 109/L [50-80 × 103/μL]). The duration of the remission is longer than 4 months during maintenance therapy with SU5416. Microvessel density in the patient's bone marrow dropped from 33.4 to 12.3 microvessels/×500-field 8 weeks after SU5416 administration and remains in the normal range. This is the first report of a stable remission achieved after administration of the RTK inhibitor SU5416 in a patient with AML relapse.
Characterization of the phosphatidylserine-exposing subpopulation of sickle cells
Authors: de Jong Kitty , Larkin Sandra K. , Styles Lori A. , Bookchin Robert M. , Kuypers Frans A.
Published: July 2002

Phosphatidylserine (PS), exclusively present in the inner monolayer of the normal red blood cell (RBC) membrane, is exposed in subpopulations of sickle cells. PS-exposing RBCs were found predominantly among the densest and the very light sickle cells. Within the light RBC fraction, PS exposure was found on reticulocytes, transferrin receptor–expressing reticulocytes, and mature RBCs. The last subset contained low-density valinomycin-resistant RBCs, previously shown to have high Na+ and low K+content. This subpopulation contained the highest percentage of PS-exposing cells. The PS-exposing sickle cells did not show the sustained high cytosolic Ca++ levels that have been shown to activate scramblase activity. Data from this study indicate that PS exposure can occur at different stages in the life of the sickle RBC and that it correlates with the loss of aminophospholipid translocase activity, the only common denominator of the PS-exposing cells. The additional requirement of scramblase activation may occur during transient increases in cytosolic Ca++.
Cross-presentation of tumor antigens by bone marrow–derived antigen-presenting cells is the dominant mechanism in the induction of T-cell tolerance during B-cell lymphoma progression
Authors: Sotomayor Eduardo M. , Borrello Ivan , Rattis Frédérique-Marie , Cuenca Alex G. , Abrams Jacob , Staveley-O'Carroll Kevin , Levitsky Hyam I.
Published: July 2002

Tumor antigen-specific T-cell tolerance may limit the efficacy of therapeutic cancer vaccines. Direct presentation of antigens by tumor cells incapable of providing adequate costimulation to tumor-specific T cells has been suggested as the basis for this unresponsiveness. Using parent-into-F1 bone marrow (BM) chimeras, this study unambiguously demonstrates that the induction of this tolerant state requires T-cell recognition of tumor antigen presented by BM-derived antigen-presenting cells (APCs), not tumor cells themselves. In the absence of host APC presentation, tumor-specific T cells remained functional, even in the setting of antigen expressed by B-cell lymphomas residing in secondary lymphoid tissues. The intrinsic APC capacity of tumor cells has therefore little influence over T-cell priming versus tolerance, a decision that is regulated at the level of host APCs.
Measles in bone marrow transplant recipients during an outbreak in São Paulo, Brazil
Authors: Machado Clarisse M. , Gonçalves Flávio B. , Pannuti Cláudio S. , Dulley Frederico L. , de Souza Vanda A. U. F.
Published: July 2002

In 1997, a measles outbreak was identified in São Paulo. Between February and December, 20 185 cases were confirmed. From April to July 1997, a seroepidemiologic survey was conducted to identify the recipients of bone marrow (BM) transplants who were susceptible to measles and the occurrence of measles in this population. A total of 156 patients were screened by enzyme immunoassay (EIA). Patients with IgG titers more than 100 mIU/mL were considered immune. Measles reimmunization records were also reviewed. Thirty-two vaccinated patients underwent serologic evaluation. Six of 22 patients (27.3%) within 3 years after vaccination lost measles immunity, in contrast to 7 of 10 patients (70%) vaccinated longer than 3 years previously (P = .049). Among the 122 nonvaccinated patients, 41 (33.6%) were susceptible to measles: 4 of 47 patients (8.5%) within the first year after BM transplantation (BMT), and 37 of the 75 patients (49.3%) after the first year after BMT (P < .001). Eight recipients acquired measles, confirmed by serology (EIA). High-avidity IgG antibodies were observed in the acute phase of measles, suggesting a secondary immune response. Measles interstitial pneumonia was observed in one patient. Seven patients had mild symptoms. Exanthema was present in all patients. All but one patient had fever and nonproductive cough. Koplik spots could be observed in 5 patients. Measles can be mild in BM transplant recipients. Exanthema is frequently present but not often typical. Immunity to measles decreases after day +365 after BMT. Additional studies are needed to evaluate the safety of measles vaccine after the first year of BMT, mostly during outbreaks.
Phase I and Pharmacologic Study of Oral ZD9331, A Novel Nonpolyglutamated Thymidylate Synthase Inhibitor, in Adult Patients With Solid Tumors
Authors: de Jonge Maja J.A. , Punt Cornelis J.A. , Sparreboom Alex , Planting André S.T. , Peters M.E.W.J. , van de Schraaf Jacqueline , Jackman Ann , Smith Rob , de Mulder Pieter H.M. , Verweij Jaap
Published: July 2002

PURPOSE: To assess the toxicity profile and dose-limiting toxicities (DLTs), to determine the maximum-tolerated dose, and to study the pharmacokinetics of ZD9331 when administered orally to patients with advanced solid tumors.

PATIENTS AND METHODS: Patients were treated with oral ZD9331 given once daily (od) or twice daily (bid) for 5, 7, or 10 days; cycles were repeated every 21 days at doses ranging from 2.5 to 40 mg. For pharmacokinetic analysis, plasma sampling was performed during the first course and assayed using a validated liquid chromatographic–tandem mass spectrometry assay. Plasma levels of 2′-deoxyuridine were measured as a surrogate marker for TS inhibition.

RESULTS: Forty-two patients received a total of 166 courses. The DLTs were myelosuppression and skin rash. Dose escalation of oral ZD9331 from 2.5 to 40 mg, as a single daily dose, resulted in a less than proportional increase in the plasma area under the concentration-time curve of ZD9331. The plasma drug exposure per cycle for the schedules 20 mg od for 5 days, 10 mg od for 10 days, and 10 mg bid for 5 days, all resulting in a total dose per cycle of 100 mg, were comparable. One partial response was noted in a patient with gastric cancer.

CONCLUSION: DLTs in this phase I study of oral ZD9331 were myelosuppression and skin toxicity. The recommended dose for phase II studies of oral ZD9331 is 20 mg od for 5 consecutive days, every 3 weeks.
Effect of Prevention Strategies on Survival and Quality-Adjusted Survival of Women With BRCA1/2 Mutations: An Updated Decision Analysis
Authors: Grann Victor R. , Jacobson Judith S. , Thomason Dustin , Hershman Dawn , Heitjan Daniel F. , Neugut Alfred I.
Published: July 2002

PURPOSE: This study updates findings regarding the effects of prophylactic surgery, chemoprevention, and surveillance on the survival and quality-adjusted survival of women who test positive for BRCA1/2 mutations.

MATERIALS AND METHODS: Markov modeling of outcomes was performed in a simulated cohort of 30-year-old women who tested positive for BRCA1/2 mutations. The model incorporated breast and ovarian cancer incidence rates from the literature and mortality rates from the Surveillance, Epidemiology, and End Results Program. Quality adjustment of survival estimates were obtained from a survey of women aged 33 to 50 years. Sensitivity analyses were performed of varied assumptions regarding timing and effects of preventive measures on cancer incidence and adverse effects.

RESULTS: A 30-year-old woman could prolong her survival beyond that associated with surveillance alone by use of preventive measures: 1.8 years with tamoxifen, 2.6 years with prophylactic oophorectomy, 4.6 years with both tamoxifen and prophylactic oophorectomy, 3.5 years with prophylactic mastectomy, and 4.9 years with both surgeries. She could prolong her quality-adjusted survival by 2.8 years with tamoxifen, 4.4 years with prophylactic oophorectomy, 6.3 years with tamoxifen and oophorectomy, and 2.6 years with mastectomy, or with both surgeries. The benefits of all of these strategies would decrease if they were initiated at later ages.

CONCLUSION: Women who test positive for BRCA1/2 mutations may derive greater survival and quality adjusted survival benefits than previously reported from chemoprevention, prophylactic surgery, or a combination. Observational studies and clinical trials are needed to verify the results of this analysis of the long-term benefits of preventive strategies among BRCA1/2-positive women.
Urinary Retention Evaluation and Catheterization Algorithm for Adult Inpatients
Authors: Chrouser Kristin , Fowler Karen E. , Mann Jason D. , Quinn Martha , Ameling Jessica , Hendren Samantha , Krapohl Greta , Skolarus Ted A. , Bernstein Steven J. , Meddings Jennifer
Published: July 2024

Importance

Acute urinary retention (UR) is common, yet variations in diagnosis and management can lead to inappropriate catheterization and harm.

Objective

To develop an algorithm for screening and management of UR among adult inpatients.

Design, Setting, and Participants

In this mixed-methods study using the RAND/UCLA Appropriateness Method and qualitative interviews, an 11-member multidisciplinary expert panel of nurses and physicians from across the US used a formal multi-round process from March to May 2015 to rate 107 clinical scenarios involving diagnosis and management of adult UR in postoperative and medical inpatients. The panel ratings informed the first algorithm draft. Semistructured interviews were conducted from October 2020 to May 2021 with 33 frontline clinicians—nurses and surgeons from 5 Michigan hospitals—to gather feedback and inform algorithm refinements.

Main Outcomes and Measures

Panelists categorized scenarios assessing when to use bladder scanners, catheterization at various scanned bladder volumes, and choice of catheterization modalities as appropriate, inappropriate, or uncertain. Next, qualitative methods were used to understand the perceived need, usability, and potential algorithm uses.

Results

The 11-member expert panel (10 men and 1 woman) used the RAND/UCLA Appropriateness Method to develop a UR algorithm including the following: (1) bladder scanners were preferred over catheterization for UR diagnosis in symptomatic patients or starting as soon as 3 hours since last void if asymptomatic, (2) bladder scanner volumes appropriate to prompt catheterization were 300 mL or greater in symptomatic patients and 500 mL or greater in asymptomatic patients, and (3) intermittent was preferred to indwelling catheterization for managing lower bladder volumes. Interview findings were organized into 3 domains (perceived need, feedback on algorithm, and implementation suggestions). The 33 frontline clinicians (9 men and 24 women) who reviewed the algorithm reported that an evidence-based protocol (1) was needed and could be helpful to clinicians, (2) should be simple and graphically appealing to improve rapid clinician review, and (3) should be integrated within the electronic medical record and prominently displayed in hospital units to increase awareness. The draft algorithm was iteratively refined based on stakeholder feedback.

Conclusions and Relevance

In this study using a systematic, multidisciplinary, evidence- and expert opinion–based approach, a UR evaluation and catheterization algorithm was developed to improve patient safety by increasing appropriate use of bladder scanners and catheterization. This algorithm addresses the need for practical guidance to manage UR among adult inpatients.
Bioelectronic Sutures with Electrochemical pH‐Sensing for Long‐Term Monitoring of the Wound Healing Progress
Authors: Kim Hwajoong , Kim Jung Hyun , Jeong Minji , Lee Dongwook , Kim Jinho , Lee Mugeun , Kim Gain , Kim Jayoung , Lee Jung Seung , Lee Jaehong
Published: July 2024

The physiological pH level at wound sites is one of the fundamental factors for monitoring wound conditions in clinical practice. To continuously assess the wound conditions, a variety of bioelectronic pH sensors are extensively developed. However, despite significant advances in bioelectronics for wound monitoring, the application of existing bioelectronic devices, primarily designed as bandages or patches, remains challenging for monitoring pH levels in deep wounds. Here, a flexible pH‐sensing suture is introduced that can be simultaneously used as both a precise pH sensor for wound monitoring and a conventional medical suture. The electrochemical pH‐sensing suture comprises Au nanoparticle‐based flexible electrodes functionalized with polyaniline for the working electrode and Ag/AgCl for the reference electrode, seamlessly integrated onto a standard medical suturing thread. This dual‐function sensing suture offers a reliable and high sensitivity of 58.9 mV pH−1, negligible hysteresis, high stability, and excellent selectivity in pH sensing. The biocompatibility of the sensing suture is systematically verified for its in vivo use. To demonstrate the capabilities of the pH‐sensing suture, it is successfully applied to an incision and chronic wound model of mouse to perform continuous and accurate monitoring of the inflammation and healing progress of the wound throughout the healing period.
Electron Beam Interaction with Carbon Nanotubes in Scanning Electron Microscope: Mechanisms and Applications
Authors: Chen Guo , Yuan Zi , Wei Yuanqi , Fu Xuze , Jiang Kaili
Published: July 2024

A comprehensive understanding of the interaction between electron beams and carbon nanotubes (CNTs) in scanning electron microscope (SEM) can be challenging due to the complex surface charging behavior and various nanostructures formed by CNTs. Herein, an overview of the challenges and potential solutions are provided for achieving high‐resolution imaging of nanomaterials, such as CNTs, in SEM systems. First, imaging mechanisms of CNTs on conducting, insulating, and hybrid substrates are summarized, with morphology, material type, and charging effect covered. Second, measuring the conductivity, bandgap, and diameter of a CNT by SEM method is introduced. Finally, the utilization of super‐aligned CNT (SACNT) films for observing insulators and vertically aligned CNT arrays (VACNTAs) as electron blackbodies are discussed separately. New techniques for imaging and characterizing nanostructures will ultimately lead to the advancement of CNT‐based technologies.
Porous GaN Nanopyramids: Advancing Beyond Conventional Nanostructures for High‐Brightness InGaN/GaN Quantum Wells Emission
Authors: Thaalbi Hamza , Kim Baul , Abdullah Ameer , Kulkarni Mandar A. , Tariq Fawad , Din Haseeb Ud , Cho Yong‐Hoon , Ryu Sang‐Wan
Published: July 2024

GaN nanostructures hold significant promise in advancing nanoscale light‐emitting devices. However, significant progress remains elusive, possibly due to the absence of innovative approaches. Beyond the smaller size of GaN nanostructures, the main interest lies in growing InGaN active layers on semi‐ and non‐polar orientations. Nevertheless, it is evident that while leveraging such a method holds initial promise, this approach may eventually reach its limits, prompting the need for fresh perspectives. In this manuscript, electrochemical etching is utilized to fabricate porous GaN nanopyramids. Given the absence of prior studies on electrochemical etching of GaN nanostructures, its etching behavior is investigated, revealing its selectivity concerning doping concentration and geometry. Furthermore, how the choice of electrolyte can differently impact the optical response of the etched template is explored. Subsequently, an InGaN/GaN quantum wells shell is grown as the active region. The significance of the approach is evidenced by a tenfold enhancement in photoluminescence emission. Porous nanopyramids demonstrate a higher internal quantum efficiency of 44.7% and faster radiative recombination time. Additionally, finite difference time domain simulation reveals a twofold increase in light extraction efficiency. This research will lead the way toward the development of a new class of nanostructures offering potential advancements in optoelectronic devices.
Multifunctional Theranostic 2D Vanadium Carbidel for Enhanced Cancer Immunotherapy
Authors: Feng Keke , Li Chenglei , Xiong Rui , Lin Yingqi , Cui Zhou , Tu Yifan , Zhang Mingzhe , Sa Baisheng , Shao Jingwei
Published: July 2024

The application of 2D MXene materials in the biomedical field has been widely explored. Apart from excellent photothermal properties, their role in modulating various immune cells and overcoming immune‐suppressive tumor microenvironments is waiting to be discovered. In this work, a novel multifunctional 2D vanadium carbide is constructed that degrades in situ in the tumor microenvironment. Various characterizations and first‐principles calculations indicated that V4C3 nanosheets exhibit excellent light absorption and photothermal conversion capabilities in the NIR‐II biological window. The photothermal and X‐ray absorption properties of V4C3 nanosheets enabled dual‐modal photoacoustic imaging/computerized tomography (PA/CT) imaging functionality. The V4C3 nanosheets in the tumor microenvironment decomposed under the effect of H2O2 and GSH, triggering a Fenton‐like reaction. The photothermal ablation and reactive oxygen species (ROS) generation capabilities enabled V4C3 nanosheets to convert cold tumors into hot ones (macrophage: M2→M1) and induce reactions like immunogenic cell death (ICD). Dendritic cell (DC) cells matured under the ICD stimulation, which promoted T cell activation, reduced Treg cells and thus effectively enhanced tumor immunotherapy. The multiple properties including imaging, photothermal, enzyme‐driven, and immune functions enable V4C3 nanosheets to ablate tumors effectively. This study provides an example for the research of the multifunctional exploration and application of MXene in biomedicine filed.
Advanced Functional Photochromic Wearables with Superior Durability and Stability for Sustainable Applications
Authors: Zhu Meng , Xu Bingang , Chen Tiandi , Zhang Junze , Sun Weiwei
Published: July 2024

The rewritable wearables based on photochromism have emerged as attractive candidates in inkless printing applications. Among various photochromic materials, polyoxometalates have great potential for rewritable wearables, with major advantages in fast response upon UV irradiation, long‐term photochemical stability, and excellent fatigue resistance. However, the development of rewritable wearables based on polyoxometalates is limited by low combining fastness, weak stability, and poor scalability. Here, a scalable strategy is reported to fabricate an ideal rewritable wearable based on fundamental charge balance mechanism. The pristine cotton substrate is grafted by cationic polymer brushes to incorporate photochromic phosphomolybdic acid (PMoA) anions through electrostatic attraction, and then the cationic surfactants with alkyl chains are introduced to encapsulate the PMoA anions to achieve charge balance subsequently. The resultant rewritable wearables display the long‐awaited properties, such as high color contrast, favorable reversibility (>10 cycles), long color retention (>15 days) and high stability against detergent and sweat (pH 6.5–8.0) during repeated washing (50 cycles) and wearing. As a demonstration, a rewritable T‐shirt is scalably fabricated, and excellent antibacterial activity and biocompatibility are demonstrated as well, which is expected to be a sustainable solution for regular fabric printing in household products and public display.
A Multifunctional Nanocomposite Hydrogel Delivery System Based on Dual‐Loaded Liposomes for Scarless Wound Healing
Authors: Xing Danlei , Xia Guoqing , Tang Xudong , Zhuang Zhiwei , Shan Jie , Fang Xiao , Qiu Le , Zha Xiaojun , Chen Xu‐Lin
Published: July 2024

Increased inflammatory responses and oxidative stress at the wound site following skin trauma impair healing. Furthermore, skin scarring places fibroblasts under severe mechanical stress and aggravates pathological fibrosis. A novel liposomal composite hydrogel is engineered for wound microenvironment remodeling, incorporating dual‐loaded liposomes into gelatin methacrylate to create a nanocomposite hydrogel. Notably, tetrahydrocurcumin (THC) and hepatocyte growth factor (HGF) are encapsulated in the hydrophobic and hydrophilic layers of liposomes, respectively. The composite hydrogel maintains porous nanoarchitecture, demonstrating sustainable THC and HGF release and enhanced mechanical properties and biocompatibility. This system effectively promotes cell proliferation and angiogenesis and attenuates apoptosis. It decreases the expression of the inflammatory factors by inhibiting the high‐mobility group box /receptor for advanced glycation end product/NF‐κB (HMGB1/RAGE/NF‐κB)pathway and increases macrophage polarization from M1 to M2 in vitro, effectively controlling inflammatory responses. It exhibits remarkable antioxidant properties by scavenging excess reactive oxygen species and free radicals. Most importantly, it effectively prevents scar formation by restraining the transforming growth factor beta (TGF‐β)/Smads pathway that downregulates associated fibrotic factors. It demonstrates strong therapeutic effects against inflammation and fibrosis in a rat skin wound model with biosafety, advancing the development of innovative hydrogel‐based therapeutic delivery strategies for clinical scarless wound therapy.
mRNA‐Engineered CD5‐CAR‐γδTCD5‐ Cells for the Immunotherapy of T‐Cell Acute Lymphoblastic Leukemia
Authors: Zhu Zhixiong , Li Hexian , Lu Qizhong , Zhang Zongliang , Li Jia , Wang Zeng , Yang Nian , Yu Zhengyu , Yang Chen , Chen Yongdong , Lu Huaqing , Wang Wei , Niu Ting , Nie Chunlai , Tong Aiping
Published: July 2024

Clinical trials of Chimeric Antigen Receptor T‐cell (CAR‐T) therapy have demonstrated remarkable success in treating both solid tumors and hematological malignancies. Nanobodies (Nbs) have emerged as promising antigen‐targeting domains for CARs, owing to their high specificity, robust stability, and strong affinity, leading to significant advancements in the field of Nb‐CAR‐T. In the realm of T‐cell acute lymphoblastic leukemia (T‐ALL) targets, CD5 stands out as a potentially excellent candidate for T‐cell‐based CAR therapy, due to its distinct expression on the surface of malignant T‐ALL cells. To mitigate graft‐versus‐host disease associated with allogeneic CAR‐T, γδT cells are selected and stimulated from peripheral blood mononuclear cells, and γδT cells are engineered via CRISPR/Cas9 to eliminate fratricide, enabling the creation of fratricide‐resistant CAR‐γδTCD5− cells. In vitro transcribed (IVT) mRNA is used to construct CAR‐T, presenting a safer, faster, and cost‐effective method compared to traditional viral vector approaches. In this study, a CD5‐VHH library is constructed, and specific CD5‐nanobodies are screened for subsequent use in CD5‐CAR‐γδTCD5− therapy. IVT‐mRNA‐CD5‐CAR‐γδTCD5− cells exhibited favorable functional characteristics and demonstrated antitumor efficacy against malignant T cell lines, underlining the potential for advancing mRNA‐CD5‐CAR‐γδTCD5− therapy.
In Situ Exsolution‐Prepared Solid‐Solution‐Type Sulfides with Intracrystal Polarization for Efficient and Selective Absorption of Low‐Frequency Electromagnetic Wave
Authors: Zeng Xiaojun , Nie Tianli , Zhao Chao , Gao Yanfeng , Liu Xiaofang
Published: July 2024

The excellent dielectric properties and tunable structural design of metal sulfides have attracted considerable interest in realizing electromagnetic wave (EMW) absorption. However, compared with traditional monometallic and bimetallic sulfides that are extensively studied, the unique physical characteristics of solid‐solution‐type sulfides in response to EMW have not been revealed yet. Herein, a unique method for preparing high‐purity solid‐solution‐type sulfides is proposed based on solid‐phase in situ exsolution of different metal ions from hybrid precursors. Utilizing CoAl‐LDH/MIL‐88A composite as a precursor, Fe0.8Co0.2S single‐phase nanoparticles are uniformly in situ formed on an amorphous substrate (denoted as CoAl), forming CoAl/Fe0.8Co0.2S heterostructure. Combing with density functional theory (DFT) calculations and wave absorption simulations, it is revealed that Fe0.8Co0.2S solid solution has stronger intracrystal polarization and electronic conductivity than traditional monometallic and bimetallic sulfides, which lead to higher dielectric properties in EM field. Therefore, CoAl/Fe0.8Co0.2S heterostructure exhibits significantly enhanced EMW absorption ability in the low‐frequency region (2–6 GHz) and can achieve frequency screening by selectively absorbing EMW of specific frequency. This work not only provides a unique method for preparing high‐purity solid‐solution‐type sulfides but also fundamentally reveals the physical essence of their excellent EMW absorption performance.