julilili42/papers huggingface dataset:
Death Receptor Ligands: New Strategies for Combined Treatment with Ionizing Radiation
2003-09-01

The major goal of modern radiation oncology is the achievement of a maximal tumor control with minimal normal tissue damage. However, normal tissue tolerance may preclude the application of tumoricidal radiation doses. In order to overcome this limitation, strategies either to increase normal tissue tolerance or to reduce the radiation dose required may prove beneficial. In this regard, attempts to minimize the required radiation dose by reducing the number of malignant clonogenic cells are promising. Therefore, therapies which induce programmed cell death (apoptosis) in tumor cells, may prove to be suitable approaches. TRAIL (TNFalpha-related apoptosis inducing ligand)/Apo2L is a very promising member of the family of death ligands. The ligand preferentially induces apoptotic cell death in a wide range of tumor cells but not in normal cells. TRAIL/Apo2L triggers apoptosis even in cells not undergoing apoptosis in response to radiation, since ionizing radiation induce apoptosis by a different pathway as death ligands although an overlapping set of molecules is involved. Combination of both modalities has been shown to induce additive or synergistic apoptotic effects and eradication of clonogenic tumor cells thereby increasing the therapeutic efficacy. The present article reviews this novel biological strategy for optimized radiotherapy based on the combination of ionizing irradiation and death receptor triggered cell death.
Limited‐disease small‐cell lung cancer
2003-09-01

Abstract Substantial improvements in treatment outcome for limited‐disease small‐cell lung cancer (LD SCLC) have been achieved in the last two decades owing to the introduction of chemotherapy (CHT) consisting of cisplatin and etoposide (PE), and the understanding that thoracic radiation therapy (TRT) is an essential component in improving treatment outcome. In addition, a recent metaanalysis confirmed the importance of prophylactic cranial irradiation (PCI) in general treatment plans for patients who show a complete response to treatment. However, numerous questions remain unanswered regarding this disease. While TRT/PE/PCI is considered to be the standard treatment in the majority of centers worldwide, the emergence of new and effective drugs (e.g., topoisomerase I inhibitors and paclitaxel) for the treatment of LD SCLC will likely affect therapy strategies in the near future. Important issues regarding optimal doses and fractionation regimens, as well as the timing of TRT, remain to be resolved. While most centers currently use b.i.d. fractionation as a result of the Intergroup findings, high‐dose standard TRT may also be beneficial. TRT volumes are also considered an important issue, since they likely relate to the incidence of both local failure and toxicity. Finally, the optimization of PCI (total dose, fractionation regimen, and timing) is already under way. The value of surgery is limited to peripheral tumors and poorly responding cancer, and to confirm histology or improve local control and survival. Semin. Surg. Oncol. 21:156–163, 2003. © 2003 Wiley‐Liss, Inc.
Self‐views in close relationships: The influence of attachment styles
2003-09-01

Two studies were conducted to test the hypothesis that self models (positive vs. negative) determine whether temporarily accessible information changes one's self‐evaluations. Regularly dating participants were led to review selectively their relationship‐related behaviours which had either favourable or unfavourable implications for their close relationships. Based on the four‐group model of attachment (secure, preoccupied, fearful, and dismissing; Bartholomew, 1990), attachment orientations were either assessed (Study 1) or activated by a guided imagination task (Study 2). The results show that participants holding a negative model of the self were more susceptible to variations in accessible information than those holding a positive model of the self. Their self‐evaluations shifted in the positive direction when positive information was salient and in the negative direction when negative information was salient. Secure and dismissing (positive self model) participants were largely unaffected by the salience manipulation. The results are discussed in light of theories that propose a dynamic self‐concept
Neue Strukturverfeinerung und Eigenschaften von Cr3C2/Structure Refinement and Properties of Cr3C2
2003-09-01

Cr 3 C 2 was obtained from arc-melting of pellets made of carbon and chromium. The structure of Cr 3 C 2 was determined by single crystal X-ray diffraction (Pnma, Z = 4, a = 553.99(6), b = 283.27(4), c = 1149.4(1) pm, R1 = 0.019 and wR2 = 0.037 for all collected reflections). The crystal structure contains isolated carbon atoms which reside inside of trigonal prismatic voids of metal atoms. The compound exhibits temperature independent paramagnetism. The electronic structure of Cr 3 C 2 has been investigated using extended Hückel calculations.
Antiangiogenesis and Radiotherapy: What Is the Role of Combined Modality Treatment?
2003-09-01

The formation of new blood vessels is a prerequisite for the growth of primary and metastatic tumour. Thus, strategies that aim at the inhibition of tumour angiogenesis have gained considerable interest in recent years. Furthermore, there is a need to identify the role of antiangiogenic agents in conjunction with conventional anticancer modalities like chemotherapy or radiotherapy. It is the objective of this review to summarise experimental data for different antiangiogenic agents used for combined modality experiments with radiotherapy. Promising data have been reported for a series of antiangiogenic agents for combined modality treatment with radiotherapy using tumour growth delay as the primary end-point. Yet, the results from different agents with various tumour lines are contradictory in part. Furthermore, enhancement of local tumour control, the main objective of curative radiotherapy, has so far been demonstrated for only two agents (DC101 and CA4DP), while experiments using TNP-470 even revealed a reduction of local tumour control when combined with irradiation. Finally, detailed studies investigating the modulation of normal tissue reactions for the combination of radiotherapy and inhibitors of angiogenesis are pending so far. Thus, experimental data currently available do not consistently support the beneficial effects of combined modality treatment with inhibitors of angiogenesis and radiotherapy. We therefore conclude that there is still a long way to go until we know which antiangiogenic agent will clinically be suitable for what tumour entity for combined treatment of radiotherapy and inhibitors of angiogenesis.
Regenerative Medicine for Diseases of the Head and Neck: Principles ofIn vivoRegeneration
2003-09-01

The application of endogenous regeneration in regenerative medicine is based on the concept of inducing regeneration of damaged or lost tissues from residual tissues in situ. Therefore, endogenous regeneration is also termed in vivo regeneration as opposed to mechanisms of ex vivo regeneration which are applied, for example, in the field of tissue engineering. The basic science foundation for mechanisms of endogenous regeneration is provided by the field of regenerative biology. The ambitious vision for the application of endogenous regeneration in regenerative medicine is stimulated by investigations in the model organisms of regenerative biology, most notably hydra, planarians and urodeles. These model organisms demonstrate remarkable regenerative capabilities, which appear to be conserved over large phylogenetical stretches with convincing evidence for a homologue origin of an endogenous regenerative capability. Although the elucidation of the molecular and cellular mechanisms of these endogenous regenerative phenomena is still in its beginning, there are indications that these processes have potential to become useful for human benefit. Such indications also exist for particular applications in diseases of the head and neck region. As such epimorphic regeneration without blastema formation may be relevant to regeneration of sensorineural epithelia of the inner ear or the olphactory epithelium. Complex tissue lesions of the head and neck as they occur after trauma or tumor resections may be approached on the basis of relevant mechanisms in epimorphic regeneration with blastema formation.
Evolution in Imperfect Commitment Bargaining – Strategic versus Ignorant Types -
2003-09-01

To commit credibly in bargaining is crucial: In the ultimatum game with its one-sided early commitment power the "proposer" gets (nearly) the whole pie while the "responder" is left with (almost) nothing. When both parties commit simultaneously the (a)symmetric Nash(1950)-bargaining solution, however, predicts (more or less) equal shares. Relying on a continuous connection of these two games by a one parameter-family of games (Fischer et al. 2003), we distinguish two behavioral dispositions, namely (1) neglecting early commitment and (2) reacting to it strategically. Based on their payoff implications we derive the evolutionarily stable behavioral disposition. This sheds new light on the hypothesis that in experiments participants neglect subtle aspects like the sequence of moves.
Methods for the in vitro determination of an individual disposition towards TH1- or TH2-reactivity by the application of appropriate stimulatory antigens
2003-09-03

SUMMARY In this study we performed several methods for the determination of cytokines (RT-PCR for the demonstration of cytokine mRNA and flow cytometry for the analysis of intracellular cytokines) and compared them with a recently established test system stimulating peripheral blood mononuclear cells (PBMC) with TH1- and TH2-relevant recall antigens and analysing type 1 and type 2 cytokines by ELISA. Aim of the study was therefore to evaluate the reliability of TH1/TH2 cytokine profiles in two individuals with different types of an allergic/atopic disposition: one of them showed a strong TH1/type 1-mediated tuberculin-reaction (subject A), the other (subject B) revealed elevated IgE-levels and eosinophil counts (TH2/type 2-mediated). PBMC were incubated with the type 1-antigen purified protein derivative (PPD) and the type 2-antigen tetanus-toxoid (TT) for seven days. From the comparison of ELISA with RT-PCR and flow cytometry-analysis it became evident that all three methods allowed the definition of subject A as a ‘type 1-responder’. Subject B showed a pure type 2-response in the ELISA method; PCR and flow cytometry analysis revealed the simultaneous production of type 1- and type 2-cytokines resulting in a mixed type 1/type 2-profile. Active immunization of subject A with TT at the end of the observation period of 12 months resulted in a transient shift from type 1- to a mixed type 1/type 2-profile (simultaneous PPD-induced IFN-γ- and TT-induced IL-5 production). From this pilot study based on clear cut clinical criteria concerning either a humoral or cellular immunological reactivity towards allergens/antigens it is suggested that the determination of type 1/type 2-cytokines by ELISA in supernatants of PBMC stimulated with type 1/type 2-relevant antigens is a useful approach for a better classification of ‘type1-’ or ‘type 2-responder’.
Spectral flow of the Dirac spectrum in intersecting vortices
2003-09-04

The spectrum of the Dirac Hamiltonian in the background of crossing vortices\\nis studied. To exploit the index theorem, and in analogy to the lattice the\\nspace-time manifold is chosen to be the four-torus . For sake of\\nsimplicity we consider two idealized cases: infinitely fat and thin\\ntransversally intersecting vortices. The time-dependent spectrum of the Dirac\\nHamiltonian is calculated and in particular the influence of the vortex\\ncrossing on the quark spectrum is investigated. For the infinitely fat\\nintersecting vortices it is found that zero modes of the four-dimensional Dirac\\noperator can be expressed in terms of those eigenspinors of the Euclidean\\ntime-dependent Dirac Hamiltonian, which cross zero energy. For thin\\nintersecting vortices the time gradient of the spectral flow of the Dirac\\nHamiltonian is steepest at the time at which the vortices cross each other.\\n
Neural correlates of laughter and humour
2003-09-05

Although laughter and humour have been constituents of humanity for thousands if not millions of years, their systematic study has begun only recently. Investigations into their neurological correlates remain fragmentary and the following review is a first attempt to collate and evaluate these studies, most of which have been published over the last two decades. By employing the classical methods of neurology, brain regions associated with symptomatic (pathological) laughter have been determined and catalogued under other diagnostic signs and symptoms of such conditions as epilepsy, strokes and circumspect brain lesions. These observations have been complemented by newer studies using modern non-invasive imaging methods. To summarize the results of many studies, the expression of laughter seems to depend on two partially independent neuronal pathways. The first of these, an 'involuntary' or 'emotionally driven' system, involves the amygdala, thalamic/hypo- and subthalamic areas and the dorsal/tegmental brainstem. The second, 'voluntary' system originates in the premotor/frontal opercular areas and leads through the motor cortex and pyramidal tract to the ventral brainstem. These systems and the laughter response appear to be coordinated by a laughter-coordinating centre in the dorsal upper pons. Analyses of the cerebral correlates of humour have been impeded by a lack of consensus among psychologists on exactly what humour is, and of what essential components it consists. Within the past two decades, however, sufficient agreement has been reached that theory-based hypotheses could be formulated and tested with various non-invasive methods. For the perception of humour (and depending on the type of humour involved, its mode of transmission, etc.) the right frontal cortex, the medial ventral prefrontal cortex, the right and left posterior (middle and inferior) temporal regions and possibly the cerebellum seem to be involved to varying degrees. An attempt has been made to be as thorough as possible in documenting the foundations upon which these burgeoning areas of research have been based up to the present time.
Analyzing changes of chromatin‐bound replication proteins occurring in response to and after release from a hypoxic block of replicon initiation in T24 cells
2003-09-09

It was shown previously [Riedinger, H. J., van Betteraey‐Nikoleit, M &amp; Probst, H. (2002) Eur. J. Biochem. 269 , 2383–2393] that initiation of in vivo SV40 DNA replication is reversibly suppressed by hypoxia in a state where viral minichromosomes exhibit a nearly complete set of replication proteins. Reoxygenation triggers fast completion and post‐translational modifications. Trying to reveal such fast changes of chromatin‐bound replication proteins in the much more complex replication of the cellular genome itself, we developed a protocol to extend these studies using the human bladder carcinoma cell line T24, which was presynchronized in G 1 by starvation. Concomitantly with stimulation of the cells by medium renewal, hypoxia was established. This treatment induced T24 cells to contain a large amount of replicons arrested in the ‘hypoxic preinitiation state’, ready to initiate replication as soon as normal pO 2 was restored. Replicons in other stages of replicative activity were not detectable. Consequently the arrested replicons were rapidly released into synchronous initiation and succeeding elongation. Extraction of T24 nuclei with a Triton X‐100 buffer yielded a fraction containing the cellular chromatin, including DNA‐bound replication proteins, while unbound proteins were removed. The usefulness of this protocol was tested by the proliferation marker PCNA. We demonstrate here that this protein switches from the remainder cellular protein pool into the Triton‐extracted nuclear fraction upon reoxygenation. Employing this protocol, analyses of chromatin‐bound MCM2, MCM3, Cdc6 and cdk2 suggests that the ‘classical’ prereplication complex is already formed during hypoxia.
Development of a fluorescent nanosensor for ribose
2003-09-10

To analyze ribose uptake and metabolism in living cells, nanosensors were engineered by flanking the Escherichia coli periplasmic ribose binding protein with two green fluorescent protein variants. Following binding of ribose, fluorescence resonance energy transfer decreased with increasing ribose concentration. Five affinity mutants were generated covering binding constants between 400 nM and 11.7 mM. Analysis of nanosensor response in COS‐7 cells showed that free ribose accumulates in the cell and is slowly metabolized. Inhibitor studies suggest that uptake is mediated by a monosaccharide transporter of the GLUT family, however, ribose taken up into the cell was not or only slowly released, indicating irreversibility of uptake.
Organization of Human Papillomavirus Productive Cycle during Neoplastic Progression Provides a Basis for Selection of Diagnostic Markers
2003-09-11

ABSTRACT The productive cycle of human papillomaviruses (HPVs) can be divided into discrete phases. Cell proliferation and episomal maintenance in the lower epithelial layers are followed by genome amplification and the expression of capsid proteins. These events, which occur in all productive infections, can be distinguished by using antibodies to viral gene products or to surrogate markers of their expression. Here we have compared precancerous lesions caused by HPV type 16 (HPV16) with lesions caused by HPV types that are not generally associated with human cancer. These include HPV2 and HPV11, which are related to HPV16 (supergroup A), as well as HPV1 and HPV65, which are evolutionarily divergent (supergroups E and B). HPV16-induced low-grade squamous intraepithelial lesions (CIN1) are productive infections which resemble those caused by other HPV types. During progression to cancer, however, the activation of late events is delayed, and the thickness of the proliferative compartment is progressively increased. In many HPV16-induced high-grade squamous intraepithelial lesions (CIN3), late events are restricted to small areas close to the epithelial surface. Such heterogeneity in the organization of the productive cycle was seen only in lesions caused by HPV16 and was not apparent when lesions caused by other HPV types were compared. By contrast, the order in which events in the productive cycle were initiated was invariant and did not depend on the infecting HPV type or the severity of disease. The distribution of viral gene products in the infected cervix depends on the extent to which the virus can complete its productive cycle, which in turn reflects the severity of cervical neoplasia. It appears from our work that the presence of such proteins in cells at the epithelial surface allows the severity of the underlying disease to be predicted and that markers of viral gene expression may improve cervical screening.
The conditional inactivation of the β-catenin gene in endothelial cells causes a defective vascular pattern and increased vascular fragility
2003-09-15

Using the Cre/loxP system we conditionally inactivated β-catenin in endothelial cells. We found that early phases of vasculogenesis and angiogenesis were not affected in mutant embryos; however, vascular patterning in the head, vitelline, umbilical vessels, and the placenta was altered. In addition, in many regions, the vascular lumen was irregular with the formation of lacunae at bifurcations, vessels were frequently hemorrhagic, and fluid extravasation in the pericardial cavity was observed. Cultured β-catenin −/− endothelial cells showed a different organization of intercellular junctions with a decrease in α-catenin in favor of desmoplakin and marked changes in actin cytoskeleton. These changes paralleled a decrease in cell–cell adhesion strength and an increase in paracellular permeability. We conclude that in vivo, the absence of β-catenin significantly reduces the capacity of endothelial cells to maintain intercellular contacts. This may become more marked when the vessels are exposed to high or turbulent flow, such as at bifurcations or in the beating heart, leading to fluid leakage or hemorrhages.
Morphology of immature stages of Prostomis mandibularis (Coleoptera: Tenebrionoidea: Prostomidae)
2003-09-15

Structural features of larvae and pupae of Prostomis mandibularis are described in detail. Larval features are discussed with respect to their functional and phylogenetic significance. The distinct asymmetry of the larval head, absence of stemmata, presence of a sensorial field on antennomere III, and elongated and broadened mandibles of pupae and adults are autapomorphies of Prostomidae. The placement of Prostomis within Tenebrionoidea is suggested by the posteriorly diverging gula with well developed gular ridges and the anterior position of the posterior tentorial arms. Affinities of Prostomidae with the pythid-pyrochroid-lineage is supported by the pad-like structure of the maxillary articulatory area, the abdominal tergite IX extending to the ventral side of the segment, and the strongly pronounced prognathous condition. Presence of a distinct molar tooth is a derived feature shared by Prostomidae, Pythidae, Pyrochroidae, Inopeplidae and Othniidae. A thorax narrower than the head and the abdomen, and a plate-like abdominal segment IX, which articulates with segment VIII, are possible synapomorphies of Prostomidae, Boridae, Mycteridae and Pyrochroidae. The strongly flattened, prognathous head and the strongly flattened body of larvae of Prostomidae are correlated with their habits of boring in wood of decaying logs.
Self-consistent solution to the nuclear many-body problem at finite temperature
2003-09-16

The properties of symmetric nuclear matter are investigated within the Green's functions approach. We have implemented an iterative procedure allowing for a self-consistent evaluation of the single-particle and two-particle propagators. The in-medium scattering equation is solved for a realistic (non-separable) nucleon-nucleon interaction including both particle-particle and hole-hole propagation. The corresponding two-particle propagator is constructed explicitely from the single-particle spectral functions. Results are obtained for finite temperatures and an extrapolation to T=0 is presented.