julilili42/papers huggingface dataset:
Architecture of the integument in lower teleostomes: Functional morphology and evolutionary implications
2002-06-20

Abstract A bony ganoid squamation is the plesiomorphic type in actinopterygians. During evolution, it was replaced by weak and more flexible elasmoid scales. We provide a comparative description of the integument of “ganoid” fishes and “nonganoid” fishes that considers all dermal components of mechanical significance (stratum compactum, morphology of ganoid scales, and their regional differences) in order to develop a functional understanding of the ganoid integument as a whole. Data were obtained for the extant “ganoid” fishes (Polypteridae and Lepisosteidae) and for closely related “lower” actinopterygians ( Acipenser ruthenus, Amia calva ) and “lower” sarcopterygians ( Latimeria chalumnae, Neoceratodus forsteri ). Body curvatures during steady undulatory locomotion, sharp turns, prey‐strikes, and fast starts in “ganoid” fishes were measured from videotapes. Extreme body curvatures as measured in anesthetized specimens are never reached during steady swimming, but are sometimes closely approached in certain situations (sharp turns, prey‐strike). During extreme body curvatures we measured high values of lateral strain on the convex and on the concave side of the body. Scale overlap changes considerably (66–127% in Lepisosteus , 42–140% in Polypterus ). The ganoid squamation forms a protective coat, but at the same time it permits extreme body curvatures. This is reflected in characteristic morphological features of the ganoid scales, such as an anterior process, concave anterior margin, and peg‐and‐socket articulation. These characters are most pronounced in the anterior body region, where maximum changes in scale overlap are required. The anterior processes and anterior concave margin, together with the attached stratum compactum, guide movements in a horizontal plane during bending. Displacements of scales relative to each other are possible for scales of different scale rows, but are impeded in scales of the same scale row due to the peg‐and‐socket articulation. Furthermore, ganoid scale rows, fibers of collagen layers of the stratum compactum, and the lateral myoseptal structures follow the same oblique orientation, which is needed to achieve extreme body curvatures. There is no evidence that body curvatures are limited by the ganoid squamation in Polypterus or Lepisosteus to any larger extent than by a type of integument devoid of ganoid scales in teleostomes of similar body shape. Our results essentially contradict former functional interpretations: 1) Ganoid scales do not especially limit body curvature during steady undulatory locomotion; 2) They do not act as torsion‐resisting devices, but may be able to damp torsion together with the stratum compactum and internal body pressure. J. Morphol. 253:290–309, 2002. © 2002 Wiley‐Liss, Inc.
Radiotherapy for medulloblastoma in children: A perspective on current international clinical research efforts
2002-06-20

Abstract Background The North America and four European pediatric cooperative groups have undertaken prospective studies for medulloblastoma continuously since the 1970s. In this article, we will review the results of these studies with respect specifically to the use of radiotherapy, and trace the developments that have led up to the present trials for patients with this tumor. Procedure Published and unpublished data from the North American CCG and POG and now COG studies, from the UKCCG and SIOP groups, as well as from the French and German groups were reviewed. Issues of especial interest included radiotherapy dose and dose fractionation schedules, scheduling of chemotherapy and radiotherapy, and technical aspects of treatment with radiotherapy that might impact on outcome. Results and Conclusions Much progress has been made in the management of medulloblastoma in childhood as a consequence of the studies undertaken sequentially by these groups over the past two decades. It now seems clear that chemotherapy plays an important role for all patients. In patients with average risk disease, the use of chemotherapy has allowed a reduction in the dose of radiotherapy to the craniospinal axis and the combination of chemotherapy with radiotherapy appears to have brought about a significant improvement in disease‐free and overall survival in this patient population. Patients with high‐risk disease fare better now than in the past as a consequence of the routine use of aggressive chemotherapy and preliminary data suggest that the use of higher doses of radiation as in the POG studies is associated with a particularly favorable outcome. Accurate delivery of radiotherapy is essential for optimal results. The avail‐ability of better tools at the treating centres and quality control as an integral part of cooperative studies are likely to bring about further improvements in outcome in the future. Med Pediatr Oncol 2002;39:99–108. © 2002 Wiley‐Liss, Inc.
Is human aging still mysterious enough to be left only to scientists?
2002-06-21

Abstract The feasibility of reversing human aging within a matter of decades has traditionally been dismissed by all professional biogerontologists, on the grounds that not only is aging still poorly understood, but also many of those aspects that we do understand are not reversible by any current or foreseeable therapeutic regimen. This broad consensus has recently been challenged by the publication, by five respected experimentalists in diverse subfields of biogerontology together with three of the present authors, of an article (Ann NY Acad Sci 959, 452–462) whose conclusion was that all the key components of mammalian aging are indeed amenable to substantial reversal (not merely retardation) in mice, with technology that has a reasonable prospect of being developed within about a decade. Translation of that panel of interventions to humans who are already alive, within a few decades thereafter, was deemed potentially feasible (though it was not claimed to be likely). If the prospect of controlling human aging within the foreseeable future cannot be categorically rejected, then it becomes a matter of personal significance to most people presently alive. Consequently, we suggest that serious public debate on this subject is now warranted, and we survey here several of the biological, social and political issues relating to it. BioEssays 24:667–676, 2002. © 2002 Wiley Periodicals, Inc.
Cytotoxic targeting of F9 teratocarcinoma tumours with anti-ED-B fibronectin scFv antibody modified liposomes
2002-06-25

We prepared small unilamellar liposomes derivatised with single chain antibody fragments specific for the ED-B domain of B-fibronectin. This extracellular matrix associated protein is expressed around newly forming blood vessels in the vicinity of many types of tumours. The single chain antibody fragments were functionalised by introduction of C-terminal cysteines and linked to liposomes via maleimide groups located at the terminal ends of poly(ethylene glycol) modified phospholipids. The properties of these anti-ED-B single chain antibody fragments-liposomes were analysed in vitro on ED-B fibronectin expressing Caco-2 cells and in vivo by studying their biodistribution and their therapeutic potential in mice bearing subcutanous F9 teratocarcinoma tumours. Radioactively labelled ((114m)Indium) single chain antibody fragments-liposomes accumulated in the tumours at 2-3-fold higher concentrations during the first 2 h after i.v. injection compared to unmodified liposomes. After 6-24 h both liposome types were found in similar amounts (8-10% injected dose g(-1)) in the tumours. Animals treated i.v. with single chain antibody fragments-liposomes containing the new cytotoxic agent 2'-deoxy-5-fluorouridylyl-N(4)-octadecyl-1-beta-D-arabinofuranosylcytosine (30 mg kg(-1) per dose, five times every 24 h) showed a reduction of tumour growth by 62-90% determined on days 5 and 8, respectively, compared to animals receiving control liposomes. Histological analysis revealed a marked reduction of F9 tumour cells and excessive deposition of fibronectin in the extracellular matrix after treatment with single chain antibody fragments-2-dioxy-5-fluorouridylyl-N(4)-octadecyl-1-beta-D-arabinofuranosylcytosine-liposomes. Single chain antibody fragments-liposomes targeted to ED-B fibronectin positive tumours therefore represent a promising and versatile novel drug delivery system for the treatment of tumours.
Note from the Editor
2002-06-25

This issue of EASTM starts with an article by Lisa Raphals comparing ancient Chinese and Greek modes of calculations and measurements and of building qualitative categories.By a precise investigation of ancient Greek geodesy and celestial measurements, as embodied in the works of Aristarchus, Archimedes, and Eratosthenes, and Chinese terrestrial and celestial measurements, described in such works as the Guanzi ~ -=r, the Classic of Mountains and Seas (Shanhai Jing 1 11 jij ~:ill ), the Springs and Autumns of Master Ui (Ui Shi chunqiu [5 5; -' §' f;}( ), the Huainunzi ift f$) -1:' .., and the Gno111on of the Zhou [dynasty] (Zhoubi
Frequencies ofGJB2mutations in German control individuals and patients showing sporadic non-syndromic hearing impairment
2002-06-27

Mutations in the GJB2 gene encoding the gap-junction protein connexin 26 have been identified in many patients with childhood hearing impairment (HI). One single mutation, 35delG (30delG), accounts for up to 70% of all analyzed European patients with autosomal recessive inherited HI and 10% of patients with HI of unknown origin, respectively. We screened 188 control individuals and 342 German patients with non-syndromic sporadic HI for the 35delG, compound heterozygosity and other GJB2 mutations by PCR, restriction enzyme based screening, SSCP and sequencing. In all patients, non-progressive hearing impairment varied from moderate to profound involving all frequencies. This study revealed one novel silent mutation (438C/T), three novel gene variants resulting in amino acid substitutions (K112E, T123S, K223R) and two novel HI-related mutations (I82M, 313del14).
Pretreatment prognostic factors and treatment results in children with hepatoblastoma
2002-06-28

Abstract BACKGROUND In the past 20 years, a dramatic improvement in the prognosis of patients with hepatoblastoma (HB) has been achieved by combining surgery with chemotherapy in several national and international trials. A worldwide, unsolved problem remains the treatment of patients with advanced or metastatic HB. METHODS The German Cooperative Pediatric Liver Tumor Study HB 94 was a prospective, multicenter, single‐arm study. The study ran from January 1994 to December 1998. The protocol assessed the efficiency of chemotherapy consisting of cisplatin, ifosfamide, and doxorubicin (CDDP/IFO/DOXO) and/or etoposide and carboplatin (VP16/CARBO). The prognostic significance of the surgical strategy, pretreatment factors, and tumor characteristics for disease free survival (DFS) were analyzed. RESULTS Sixty‐nine children with HB were treated in the HB 94 study. The median follow‐up of survivors was 58 months (range, 32–93 months). Fifty‐three of 69 patients (77%) remained alive, and 16 of 69 patients (23%) died. Long‐term DFS was as follows: 26 of 27 patients had Stage I HB, 3 of 3 patients had Stage II HB, 19 of 25 patients had Stage III HB, and 5 of 14 patients had Stage IV. A complete resection of the primary tumor was achieved in 54 of 63 patients (86%). Six children (8%) had no surgical treatment. Twenty‐two tumors were resected primarily, and 41 children underwent surgery after initial chemotherapy. Two children underwent liver transplantation. There was no perioperative death. Forty‐eight children received primary chemotherapy with CDDP/IFO/DOXO. Forty‐one of 48 children achieved partial remission after CDDP/IFO/DOXO. Eighteen children with advanced or recurrent HB underwent VP16/CARBO chemotherapy, with a response achieved by 12 children. The relevant pretreatment prognostic factors were growth pattern of the liver tumor ( P = 0.0135), vascular tumor invasion ( P = 0.0039), occurrence of distant metastases ( P = 0.0001), initial α‐fetoprotein level ( P = 0.0034), and surgical radicality ( P &lt; 0.0001). CONCLUSIONS The current results underline the necessity of preoperative chemotherapy in all children with HB. Complete tumor resection is one of the main prognostic factors. Cancer 2002;95:172–82. © 2002 American Cancer Society. DOI 10.1002/cncr.10632
Fluxon modes in intrinsic Josephson junctions in Bi2Sr2CaCu2O8 single crystals
2002-06-28

We present experimental investigations of collective resonant Josephson fluxon modes in intrinsic Josephson junction stacks realized as long mesa structures on Bi2Sr2CaCu2O8 single crystals. The mesas consisted of three to six intrinsically stacked junctions. They were between 0.6 and 1 μm wide, and their length was between 6 and 8 μm. In external magnetic fields oriented parallel to the layers, the current–voltage characteristics of the 0.5 μm wide mesas exhibited pronounced resonant structures while for the wider structures the resonances were absent or at most weakly developed. We analyse our results in terms of one-dimensional coupled sine-Gordon equations describing the dynamics of stacked Josephson junctions.
Transverse Flow of Kaons in Heavy-Ion Collisions
2002-06-28

The transverse flow of positively charged kaons from heavy-ion collisions at intermediate energy is investigated within the framework of the quantum molecular dynamics model. The calculated results show that the experimental data are only consistent with those including the kaon mean-field potential from the chiral Lagrangian. This indicates that the transverse flow pattern of kaons is a useful probe of the kaon potential in a nuclear medium.
Trichome morphogenesis: a cell–cycle perspective
2002-06-29

Arabidopsis leaf hairs (trichomes) are polyploid epidermal cells with a predictable branching pattern. More than 15 genes have been identified that are involved in the regulation of branching. The cloning of the ZWICHEL , ANGUSTIFOLIA and STICHEL genes points to two mechanistic aspects of branch formation: (i) a role of the microtubule cytoskeleton; and (ii) a link to the regulation of cell divisions. The latter aspect is supported by the recent identification of an Arabidopsis mutant with multicellular trichomes, the siamese mutant, suggesting that Arabidopsis trichomes are evolutionarily derived from multicellular forms. We speculate that the spatial information for branch formation is derived from mechanisms employed in cell divisions.
The Arabidopsis BODENLOS gene encodes an auxin response protein inhibiting MONOPTEROS-mediated embryo patterning
2002-07-01

Developmental responses to the plant hormone auxin are thought to be mediated by interacting pairs from two protein families: short-lived inhibitory IAA proteins and ARF transcription factors binding to auxin-response elements. monopteros mutants lacking activating ARF5 and the auxin-insensitive mutant bodenlos fail to initiate the root meristem during early embryogenesis. Here we show that the bodenlos phenotype results from an amino-acid exchange in the conserved degradation domain of IAA12. BODENLOS and MONOPTEROS interact in the yeast two-hybrid assay and the two genes are coexpressed in early embryogenesis, suggesting that BODENLOS inhibits MONOPTEROS action in root meristem initiation.
TheWUSCHELandSHOOTMERISTEMLESSgenes fulfil complementary roles inArabidopsisshoot meristem regulation
2002-07-01

Continuous organ formation from the shoot apical meristem requires the integration of two functions: a set of undifferentiated, pluripotent stem cells is maintained at the very tip of the meristem, while their daughter cells in the periphery initiate organ primordia. The homeobox genes WUSCHEL (WUS) and SHOOTMERISTEMLESS (STM) encode two major regulators of meristem formation and maintenance in Arabidopsis, yet their interaction in meristem regulation is presently unclear. Here, we have addressed this question using loss- and gain-of-function approaches. We show that stem cell specification by WUS does not require STM activity. Conversely, STM suppresses differentiation independently of WUS and is required and sufficient to promote cell division. Consistent with their independent and distinct phenotypic effects, ectopic WUS and STM activities induce the expression of different downstream target genes. Finally, the pathways regulated by WUS and STM appear to converge in the suppression of differentiation, since coexpression of both genes produced a synergistic effect, and increased WUS activity could partly compensate for loss of STM function. These results suggest that WUS and STM share labour in the shoot apical meristem: WUS specifies a subset of cells in the centre as stem cells, while STM is required to suppress differentiation throughout the meristem dome, thus allowing stem cell daughters to be amplified before they are incorporated into organs.
Metastatic pathways and time courses in the orderly progression of cutaneous melanoma
2002-07-01

The time course of the development of distant metastasis was more or less the same irrespective of the metastatic pathway; this suggests that in patients with in-transit or satellite metastasis or regional lymph node metastasis, haematogenic metastatic spread had already taken place. Thus, the diagnostic value of sentinel lymph node biopsy and the therapeutic benefit of elective lymph node dissection may be limited, as satellite and in-transit metastases or direct distant metastases will not be detected and haematogenous spread may already have taken place when the intervention is performed.
Aversive Pavlovian conditioning in psychopaths: Peripheral and central correlates
2002-07-01

Differential aversive Pavlovian conditioning with a foul odor as unconditioned stimulus (US) and neutral faces as conditioned stimuli (CS) was compared between 9 noncriminal psychopaths as defined by the Hare Psychopathy Checklist Revised and 12 healthy controls. Event-related potentials (ERP), heart rate, skin conductance response, corrugator EMG, and startle response potentiation as well as valence, arousal, and contingency of the CS were assessed. Whereas the healthy controls (HC) showed significant CS +/CS- differentiation, the psychopaths (PP) failed to exhibit a conditioned response although unconditioned responses were comparable between the groups. N100, P200, and P300 to the CSs revealed that psychopaths were not deficient in information processing and showed even better anticipatory responding than the HC group indicated by the terminal contingent negative variation (tCNV), that lacked, however, CS+ and CS- differentiation. These data indicate a deficit in association formation in psychopaths that may be related to deficient interaction of limbic-subcortical and cortical structures.
Aversive Pavlovian conditioning in psychopaths: Peripheral and central correlates
2002-07-01

Differential aversive Pavlovian conditioning with a foul odor as unconditioned stimulus (US) and neutral faces as conditioned stimuli (CS) was compared between 9 noncriminal psychopaths as defined by the Hare Psychopathy Checklist Revised and 12 healthy controls. Event‐related potentials (ERP), heart rate, skin conductance response, corrugator EMG, and startle response potentiation as well as valence, arousal, and contingency of the CS were assessed. Whereas the healthy controls (HC) showed significant CS+/CS− differentiation, the psychopaths (PP) failed to exhibit a conditioned response although unconditioned responses were comparable between the groups. N100, P200, and P300 to the CSs revealed that psychopaths were not deficient in information processing and showed even better anticipatory responding than the HC group indicated by the terminal contingent negative variation (tCNV), that lacked, however, CS+ and CS− differentiation. These data indicate a deficit in association formation in psychopaths that may be related to deficient interaction of limbic‐subcortical and cortical structures.
Dynamics of Gamma-Band Activity during an Audiospatial Working Memory Task in Humans
2002-07-01

The representation of visual objects in short-term memory has been shown to be related to increased gamma-band activity in the electroencephalogram. Using a similar paradigm, we investigated oscillatory magnetoencephalographic activity in human subjects during a delayed matching-to-sample task requiring working memory of auditory spatial information. The memory task involved same-different judgments about the lateralization angle of pairs of filtered noise stimuli (S1 and S2) separated by 800 msec delays of background noise. This was compared with a control condition requiring the detection of a possible change in the background noise volume appearing instead of S2 (volume task). Statistical probability mapping revealed increased spectral activity at 59 Hz over left parietal cortex during the delay phase of the memory condition. In addition, 59 Hz coherence was enhanced between left parietal and right frontal sensors. During the end of the delay and during the presentation of S2, enhanced gamma-band activity at 67 Hz was observed over right frontal and later over midline parietal areas. In contrast, the volume task was characterized by increased left inferior frontotemporal 59 Hz spectral amplitude after S1. Apparently representation of the spatial position of a sound source is associated both with synchronization of networks in parietal areas involved in the auditory dorsal stream and with increased coupling between networks serving representation of audiospatial information and frontal executive systems. The comparison with S2 seemed to activate frontal and parietal neuronal ensembles. Gamma-band activity during the volume task may reflect auditory pattern encoding in auditory ventral stream areas.
Molecular Mechanisms of Polymorphic CYP3A7 Expression in Adult Human Liver and Intestine
2002-07-01

Human CYP3A enzymes play a pivotal role in the metabolism of many drugs, and the variability of their expression among individuals may have a strong impact on the efficacy of drug treatment. However, the individual contributions of the four CYP3A genes to total CYP3A activity remain unclear. To elucidate the role of CYP3A7, we have studied its expression in human liver and intestine. In both organs, expression of CYP3A7 mRNA was polymorphic. The recently identified CYP3A7*1C allele was a consistent marker of increased CYP3A7 expression both in liver and intestine, whereas the CYP3A7*1B allele was associated with increased CYP3A7 expression only in liver. Because of the replacement of part of the CYP3A7 promoter by the corresponding region of CYP3A4, the CYP3A7*1C allele contains the proximal ER6 motif of CYP3A4. The pregnane X and constitutively activated receptors were shown to bind with higher affinity to CYP3A4-ER6 than to CYP3A7-ER6 motifs and transactivated only promoter constructs containing CYP3A4-ER6. Furthermore, we identified mutations in CYP3A7*1C in addition to the ER6 motif that were necessary only for activation by the constitutively activated receptor. We conclude that the presence of the ER6 motif of CYP3A4 mediates the high expression of CYP3A7 in subjects carrying CYP3A7*1C.