julilili42/papers huggingface dataset:
Randomized Phase III Study of Temozolomide Versus Dacarbazine in the Treatment of Patients With Advanced Metastatic Malignant Melanoma
2000-01-01

PURPOSE: : To compare, in 305 patients with advanced metastatic melanoma, temozolomide and dacarbazine (DTIC) in terms of overall survival, progression-free survival (PFS), objective response, and safety, and to assess health-related quality of life (QOL) and pharmacokinetics of both drugs and their metabolite, 5-(3-methyltriazen-1-yl)imidazole-4-carboximide (MTIC). PATIENTS AND METHODS: Patients were randomized to receive either oral temozolomide at a starting dosage of 200 mg/m 2 /d for 5 days every 28 days or intravenous (IV) DTIC at a starting dosage of 250 mg/m 2 /d for 5 days every 21 days. RESULTS: In the intent-to-treat population, median survival time was 7.7 months for patients treated with temozolomide and 6.4 months for those treated with DTIC (hazards ratio, 1.18; 95% confidence interval [CI], 0.92 to 1.52). Median PFS time was significantly longer in the temozolomide-treated group (1.9 months) than in the DTIC-treated group (1.5 months) (P = .012; hazards ratio, 1.37; 95% CI, 1.07 to 1.75). No major difference in drug safety was observed. Temozolomide was well tolerated and produced a noncumulative, transient myelosuppression late in the 28-day cycle. The most common nonhematologic toxicities were mild to moderate nausea and vomiting, which were easily managed. Temozolomide therapy improved health-related QOL; more patients showed improvement or maintenance of physical functioning at week 12. Systemic exposure (area under the curve) to the parent drug and the active metabolite, MTIC, was higher after treatment with oral temozolomide than after IV administration of DTIC. CONCLUSION: Temozolomide demonstrates efficacy equal to that of DTIC and is an oral alternative for patients with advanced metastatic melanoma.
In vivo application of RNA leads to induction of specific cytotoxic T lymphocytes and antibodies
2000-01-01

To study the efficiency of RNA-based vaccines, RNA coding for the model antigen beta-galactosidase (beta-gal) was transcribed in vitro from a lacZ gene flanked by stabilizing Xenopus laevis beta-globin 5' and 3' sequences and was protected from RNase degradation by condensation with the polycationic peptide protamine. The liposome-encapsulated condensed RNA-peptide complex, the condensed RNA-peptide complex without liposome or naked, unprotected RNA, was injected into BALB/c (H-2(d)) mice. All preparations led to protein expression in the local tissue, activation of L(d)-restricted specific cytotoxic T lymphocytes (CTL) and production of IgG antibodies reactive against beta-gal. RNA-triggered CTL were as efficient in the lysis of lacZ-transfected target cells as CTL triggered by a lacZ-DNA eukaryotic expression vector. Immunization with RNA transcribed from a cDNA library from the beta-gal-expressing cell line P13.1 again led to beta-gal-specific CTL and IgG induction. Thus, both naked and protected RNA can be used to elicit a specific immune response in vivo, whereby the protected RNA is stable in vitro for a longer period of time. RNA vaccines can be produced in high amounts and have the same major advantages as DNA vaccines but lack the potentially harmful effect of DNA integration into the genome.
Involvement of the choroid plexus in central nervous system inflammation
2000-01-01

During inflammatory conditions in the central nervous system (CNS), immune cells immigrate into the CNS and can be detected in the CNS parenchyma and in the cerebrospinal fluid (CSF). The most comprehensively investigated model for CNS inflammation is experimental autoimmune encephalomyelitis (EAE), which is considered the prototype model for the human disease multiple sclerosis (MS). In EAE autoagressive CD4+, T cells gain access to the CNS and initiate the molecular and cellular events leading to edema, inflammation, and demyelination in the CNS. The endothelial blood-brain barrier (BBB) has been considered the obvious place of entry for the circulating immune cells into the CNS. A role of the choroid plexus in the pathogenesis of EAE or MS, i.e., as an alternative entry site for circulating lymphocytes directly into the CSF, has not been seriously considered before. However, during EAE, we observed massive ultrastructural changes within the choroid plexus, which are different from changes observed during hypoxia. Using immunohistochemistry and in situ hybridization, we observed expression of VCAM-1 and ICAM-1 in the choroid plexus and demonstrated their upregulation and also de novo expression of MAdCAM-1 during EAE. Ultrastructural studies revealed polar localization of ICAM-1, VCAM-1, and MAdCAM-1 on the apical surface of choroid plexus epithelial cells and their complete absence on the fenestrated endothelial cells within the choroid plexus parenchyme. Furthermore, ICAM-1, VCAM-1, and MAdCAM-1 expressed in choroid plexus epithelium mediated binding of lymphocytes via their known ligands. In vitro, choroid plexus epithelial cells can be induced to express ICAM-1, VCAM-1, MAdCAM-1, and, additionally, MHC class I and II molecules on their surface. Taken together, our observations imply a previously unappreciated function of the choroid plexus in the immunosurveillance of the CNS. Microsc. Res. Tech. 52:112–129, 2001. © 2001 Wiley-Liss, Inc.
Differential regulation of three functional ammonium transporter genes by nitrogen in root hairs and by light in leaves of tomato
2000-01-01

Summary To elucidate the role of transporters in N nutrition of tomato, two new transporter genes were isolated from cDNA libraries of root hairs or leaves of tomato. While LeAMT1;2 is closely related to LeAMT1;1 (75.6% amino acid identity), LeAMT1;3 is more distantly related (62.8% identity) and possesses two short upstream open reading frames in the 5′ end of the mRNA and a particularly short N‐terminus of the protein as unique features. When expressed in yeast mutants defective in uptake, all three genes complemented uptake. In roots of hydroponically grown plants, transcript levels of LeAMT1;2 increased after or NO 3 – supply, while LeAMT1;1 was induced by N deficiency coinciding with low glutamine concentrations, and LeAMT1;3 was not detected. In aeroponic culture, expression of LeAMT1;1 and LeAMT1;2 was higher in root hairs than in the remaining root fraction. Growth of plants at elevated CO 2 slightly decreased expression of LeAMT1;2 and LeAMT1;3 in leaves, but strongly repressed transcript levels of chloroplast glutamine synthetase and photorespiratory serine hydroxymethyl‐transferase. Expression of LeAMT1;2 and LeAMT1;3 showed a reciprocal diurnal regulation with highest transcript levels of LeAMT1;3 in darkness and highest levels of LeAMT1;2 after onset of light. These results indicate that in tomato at least two high‐affinity transporters, LeAMT1;1 and LeAMT1;2, are differentially regulated by N and contribute to root hair‐mediated acquisition from the rhizosphere. In leaves, the reciprocally expressed transporters LeAMT1;2 and LeAMT1;3 are supposed to play different roles in N metabolism, uptake and/or NH 3 retrieval during photorespiration.
Residual based a posteriori error estimators for eddy current computation
2000-01-01

We consider H(curl;Ω)-elliptic problems that have been discretized by means of Nédélec's edge elements on tetrahedral meshes. Such problems occur in the numerical computation of eddy currents. From the defect equation we derive localized expressions that can be used as a posteriori error estimators to control adaptive refinement. Under certain assumptions on material parameters and computational domains, we derive local lower bounds and a global upper bound for the total error measured in the energy norm. The fundamental tool in the numerical analysis is a Helmholtz-type decomposition of the error into an irrotational part and a weakly solenoidal part.
Functional Relationship Among Medial Prefrontal Cortex, Nucleus Accumbens, and Ventral Tegmental Area in Locomotion and Reward
2000-01-01

Prominent projections of the medial prefrontal cortex (mPFC) to the nucleus accumbens (NAS) and the ventral tegmental area (VTA) exist, but it has been difficult to assign a clear functional role to either of these projections. With some exceptions to be discussed in some detail, only a few neurochemical and behavioral effects of manipulating the mPFC can be explained by invoking the mPFC-NAS projection, while most effects are compatible with an involvement of the mPFC-VTA-NAS or mPFC-pedunculopontine tegmental nucleus (PPTg)-VTA-NAS circuits. What is known about the organization and function of these loops is generally consistent with the results obtained by stimulating or lesioning or injecting drugs into the mPFC, yet these findings are largely inconsistent with the functional organization of the mPFC-NAS projection. This review briefly summarizes some of the most important aspects of what is known about the functional interactions of the mPFC. NAS, VTA, and associated areas, and focuses on functional differences between the mesocortical and the mesoaccumbal dopaminergic projections, and between the corticomesencephalic and the corticoaccumbal glutamatergic projections.
Attitudinal Ambivalence
2000-01-01

The concept of attitudinal ambivalence refers to the degree to which an attitude object is evaluated positively and negatively at the same time. As is argued in the present chapter, ambivalence is an aspect of attitude strength which is likely to have consequences with respect to its impact on information processing, the persistence of the respective attitude, its resistance to persuasion, as well as the relationship between the attitude and relevant behavior. For example, attitudes are assumed to be less temporarily stable and to correspond less well with pertinent behaviors at higher levels of ambivalence. However, depending upon which operational approach to measuring ambivalence is adopted, different processes and consequences are to be expected. Our hypotheses are discussed in the light of relevant research.
Color Duplex Measurement of Cerebral Blood Flow Volume in Healthy Adults
2000-01-01

Background and Purpose —Global cerebral blood flow (CBF) is an important yet largely unknown quantity in the treatment of neurological intensive care patients. Color duplex sonography of the extracranial cerebral arteries can be used to measure global CBF volume directly at the bedside. To establish reference data on global CBF volume and to test the influence of sex and age on this parameter, a prospective study was performed in a group of 78 healthy adults aged 20 to 85 years (39 women, 39 men; mean age, 52±19 years in either sex). Methods —The common, external, and internal carotid arteries and the vertebral arteries were examined with the use of a 7.0-MHz transducer of a computed sonography system. Angle-corrected time-averaged flow velocity and the diameter of the vessel were measured. Intravascular flow volumes were calculated as the product of angle-corrected time-averaged flow velocity and the cross-sectional area of the circular vessel. CBF volume was determined as the sum of flow volumes in the internal carotid and vertebral arteries of both sides. Results —From 20 to 85 years of age, CBF volume decreased significantly ( P ≤0.0001), on average by ≈3 mL/min per year. There were no sex-linked differences in CBF volume. The mean relative contributions of the internal carotid artery and the vertebral arteries to global CBF volume remained constant with age (76% versus 24%). The reference data on CBF volume established for the groups aged 20 to 39 years, 40 to 59 years, and 60 to 85 years were 727±102, 656±121, and 603±106 mL/min, respectively. Conclusions —The data presented here provide additional information on the natural development of global cerebral perfusion in “benign aging.” CBF volume reference data for different age groups were also established. These data provide a basis for the clinical application of CBF volume measurements at the bedside, especially in the monitoring of CBF volume in neurological intensive care patients.
Mirror symmetry and toric degenerations of partial flag manifolds
2000-01-01

In this paper we propose and discuss a mirror construction for complete intersections in partial flag manifolds F (n1, . . . , nl, n). This construction includes our previous mirror construction for complete intersection in Grassmannians and the mirror construction of Givental for complete flag manifolds. The key idea of our construction is a degeneration of F (n1, . . . , nl, n) to a certain Gorenstein toric Fano variety P (n1, . . . , nl, n) which has been investigated by Gonciulea and Lakshmibai. We describe a natural small crepant desingularization of P (n1, . . . , nl, n) and prove a generalized version of a conjecture of Gonciulea and Lakshmibai on the singular locus of P (n1, . . . , nl, n). Mathematisches Institut, Eberhard-Karls-Universitat Tubingen, D-72076 Tubingen, Germany, email address: batyrev@bastau.mathematik.uni-tuebingen.de Department of Mathematics, Oklahoma State University, Stillwater, OK 74078, USA email address: ciocan@math.okstate.edu Department of Mathematics, University of California Davis, Davis, CA 95616, USA email address: bumsig@math.ucdavis.edu FB 17, Mathematik, Johannes Gutenberg-Universitat Mainz, D-55099 Mainz, Germany, email address: straten@mathematik.uni-mainz.de
The heat shock protein gp96 induces maturation of dendritic cells and down-regulation of its receptor
2000-01-01

Peptides associated with the heat shock protein gp96 induce a specific T cell response against cells from which gp96 is isolated. Recently, we have shown that gp96 binds to a yet unknown receptor present on dendritic cells (DC) and that receptor-mediated uptake is required for cross-presentation of gp96-associated peptides by DC. We now describe that gp96 mediates maturation of DC as determined by up-regulation of MHC class II and CD86 molecules, secretion of the cytokines IL-12 and TNF-alpha and enhanced T cell stimulatory capacity. Heat-denatured gp96 is not able to induce DC maturation and cytokine secretion. Furthermore, we show that mature DC are no longer able to bind gp96 molecules. Hence, the gp96 receptor is down-regulated on mature DC, suggesting that this receptor behaves similar to other receptors involved in antigen uptake like the scavenger receptor CD36, the mannose receptor or the integrins alpha(v)beta(3) and alpha(v)beta(5). Together, our findings provide an additional explanation for the remarkable immunogenicity of gp96 as a cross-priming antigen carrier and direct activator of DC.
Cell Volume in the Regulation of Cell Proliferation and Apoptotic Cell Death
2000-01-01

Cell proliferation must - at some time point - lead to increase of cell volume and one of the hallmarks of apoptosis is cell shrinkage. At constant extracellular osmolarity those alterations of cell volume must reflect respective changes of cellular osmolarity which are hardly possible without the participation of cell volume regulatory mechanisms. Indeed, as shown for ras oncogene expressing 3T3 fibroblasts, cell proliferation is paralleled by activation of Na(+)/H(+) exchange and Na(+),K(+),2Cl(-) cotransport, the major transport systems accomplishing regulatory cell volume increase. Conversely, as evident from CD95-induced apoptotic cell death, apoptosis is paralleled by inhibition of Na(+)/H(+) exchanger and by activation of Cl(-) channels and release of the organic osmolyte taurine, major components of regulatory cell volume decrease. However, ras oncogene activation leads to activation and CD95 receptor triggering to inhibition of K(+) channels. The effects counteract the respective cell volume changes. Presumably, they serve to regulate cell membrane potential, which is decisive for Ca(++) entry through I(CRAC) and the generation of cytosolic Ca(++) oscillations in proliferating cells. As a matter of fact I(CRAC) is activated in ras oncogene expressing cells and inhibited in CD95-triggered cells. Activation of K(+) channels and Na(+)/H(+) exchanger as well as Ca(++) oscillations have been observed in a wide variety of cells upon exposure to diverse mitogenic factors. Conversely, diverse apoptotic factors have been shown to activate Cl(-) channels and organic osmolyte release. Inhibition of K(+) channels is apparently, however, not a constant phenomenon paralleling apoptosis which in some cells may even require the operation of K(+) channels. Moreover, cell proliferation may at some point require activation of Cl(-) channels. In any case, the alterations of cell volume are obviously important for the outcome, as cell shrinkage impedes cell proliferation and apoptosis can be elicited by increase of extracellular osmolarity. At this stage little is known about the interplay of cell volume regulatory mechanisms and the cellular machinery leading to mitosis or death of the cell. Thus, considerable further experimental effort is required in this exciting area of cell physiology.
The Use of Xenopus laevis Oocytes for the Functional Characterization of Heterologously Expressed Membrane Proteins
2000-01-01

The oocytes of the South African clawed frog X. laevis are widely used for the expression of heterologous proteins. The functional characterization of membrane proteins in particular has significantly profited from the use of this expression system. Heterologous cRNA can easily be injected and protein expression and function be studied with several techniques. This review will give a short overview into the variety of methods applicable. They span from different electrophysiological methods such as two electrode voltage clamp, patch clamp and ion-selective electrodes over cytochemistry to protein biochemistry. In spite of the wide usage of Xenopus oocytes, caution should be taken interpreting the results of protein expression. Heterologous proteins may either interact with endogenous proteins, the background of endogenous protein function may be relatively high, or altered protein behaviour may occur due to differences of the ambient temperature or altered cellular environment.
A practical evaluation of popular volume rendering algorithms
2000-01-01

Article Free Access Share on A practical evaluation of popular volume rendering algorithms Authors: Michael Meißner Department of Computer Science, University of Tübingen, Germany Department of Computer Science, University of Tübingen, GermanyView Profile , Jian Huang Department of Computer Science, The Ohio State University, Columbus Department of Computer Science, The Ohio State University, ColumbusView Profile , Dirk Bartz Department of Computer Science, University of Tübingen, Germany Department of Computer Science, University of Tübingen, GermanyView Profile , Klaus Mueller Department of Computer Science, State University of New York at Stony Brook Department of Computer Science, State University of New York at Stony BrookView Profile , Roger Crawfis Deartment of Computer Science, The Ohio State University, Columbus Deartment of Computer Science, The Ohio State University, ColumbusView Profile Authors Info & Claims VVS '00: Proceedings of the 2000 IEEE symposium on Volume visualizationOctober 2000 Pages 81–90https://doi.org/10.1145/353888.353903Online:09 October 2000Publication History 71citation922DownloadsMetricsTotal Citations71Total Downloads922Last 12 Months47Last 6 weeks7 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
Cutting Edge: Signal-Regulatory Protein β1 Is a DAP12-Associated Activating Receptor Expressed in Myeloid Cells
2000-01-01

Abstract Signal-regulatory proteins (SIRPs) are cell-surface glycoproteins expressed on myeloid and neural cells that have been shown to recruit SH2 domain-containing protein phosphatase 1 (SHP-1) and SHP-2 and to regulate receptor tyrosine kinase-coupled signaling. One SIRP of unknown function, designated SIRPβ1, contains a short cytoplasmic domain that lacks sequence motifs capable of recruiting SHP-1 and SHP-2. Using a SIRP-specific mAb, we show that SIRPβ1 is expressed in monocytes and dendritic cells and associates with the signal transduction molecule DAP12. SIRPβ1/DAP12 complex formation was required for efficient cell-surface expression of SIRPβ1. Stimulation of this complex induced tyrosine phosphorylation, mitogen-activated protein kinase activation, and cellular activation. Thus, SIRPβ1 is a new DAP12-associated receptor involved in the activation of myeloid cells.
Functional Imaging of Conditioned Aversive Emotional Responses in Antisocial Personality Disorder
2000-01-01

Individuals with antisocial personality disorder (n = 12) and healthy controls (n = 12) were examined for cerebral regional activation involved in the processing of negative affect. A differential aversive classical conditioning paradigm was applied with odors as unconditioned stimuli and faces as conditioned stimuli. Functional magnetic resonance imaging (fMRI) based on echo-planar imaging was used while cerebral activity was studied during habituation, acquisition, and extinction. Individually defined cerebral regions were analyzed. Both groups indicated behavioral conditioning following subjective ratings of emotional valence to conditioned stimuli. Differential effects were found during acquisition in the amygdala and dorsolateral prefrontal cortex. Controls showed signal decreases, patients signal increases. These preliminary results revealed unexpected signal increases in cortical/subcortical areas of patients. The increases may result from an additional effort put in by these individuals to form negative emotional associations, a pattern of processing that may correspond to their characteristic deviant emotional behavior.
Crystal structure of the antibiotic albomycin in complex with the outer membrane transporter FhuA
2000-01-01

Abstract One alternative method for drug delivery involves the use of siderophore‐antibiotic conjugates. These compounds represent a specific means by which potent antimicrobial agents, covalently linked to iron‐chelating siderophores, can be actively transported across the outer membrane of Gram‐negative bacteria. These “Trojan Horse” antibiotics may prove useful as an efficient means to combat multi‐drug–resistant bacterial infections. Here we present the crystallo‐graphic structures of the natural siderophore‐antibiotic conjugate albomycin and the siderophore phenylferricrocin, in complex with the active outer membrane transporter FhuA from Escherichia coli. To our knowledge, this represents the first structure of an antibiotic bound to its cognate transporter. Albomycins are broad‐host range antibiotics that consist of a hydroxamate‐type iron‐chelating siderophore, and an antibiotically active, thioribosyl pyrimidine moiety. As observed with other hydroxamate‐type siderophores, the three‐dimensional structure of albomycin reveals an identical coordination geometry surrounding the ferric iron atom. Unexpectedly, this antibiotic assumes two conformational isomers in the binding site of FhuA, an extended and a compact form. The structural information derived from this study provides novel insights into the diverse array of antibiotic moieties that can be linked to the distal portion of iron‐chelating siderophores and offers a structural platform for the rational design of hydroxamate‐type siderophore‐antibiotic conjugates.