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Showing papers by "Free University of Berlin published in 2001"


Journal ArticleDOI
TL;DR: An overview about the selection of the ingredients, different ways of SLN production and SLN applications, and the in vivo fate of the carrier are presented.

2,786 citations


Journal ArticleDOI
21 Jun 2001-Nature
TL;DR: The crystal structure of photosystem I from the thermophilic cyanobacterium Synechococcus elongatus described in this paper provides a picture at atomic detail of 12 protein subunits and 127 cofactors comprising 96 chlorophylls, 2 phylloquinones, 3 Fe4S4 clusters, 22 carotenoids, 4 lipids, a putative Ca2+ ion and 201 water molecules.
Abstract: Life on Earth depends on photosynthesis, the conversion of light energy from the Sun to chemical energy. In plants, green algae and cyanobacteria, this process is driven by the cooperation of two large protein-cofactor complexes, photosystems I and II, which are located in the thylakoid photosynthetic membranes. The crystal structure of photosystem I from the thermophilic cyanobacterium Synechococcus elongatus described here provides a picture at atomic detail of 12 protein subunits and 127 cofactors comprising 96 chlorophylls, 2 phylloquinones, 3 Fe4S4 clusters, 22 carotenoids, 4 lipids, a putative Ca2+ ion and 201 water molecules. The structural information on the proteins and cofactors and their interactions provides a basis for understanding how the high efficiency of photosystem I in light capturing and electron transfer is achieved.

2,237 citations


Journal ArticleDOI
TL;DR: The paper focuses on the loading of the femoral implant component but complete data are additionally stored on an associated compact disc that contains complete gait and hip contact force data as well as calculated muscle activities during walking and stair climbing and the frequencies of daily activities observed in hip patients.

2,028 citations


Journal ArticleDOI
08 Feb 2001-Nature
TL;DR: The X-ray structure of photosystem II is described on the basis of crystals fully active in water oxidation, shows how protein subunits and cofactors are spatially organized and the larger subunits are assigned and the locations and orientations of the cofacters are defined.
Abstract: Oxygenic photosynthesis is the principal energy converter on earth. It is driven by photosystems I and II, two large protein-cofactor complexes located in the thylakoid membrane and acting in series. In photosystem II, water is oxidized; this event provides the overall process with the necessary electrons and protons, and the atmosphere with oxygen. To date, structural information on the architecture of the complex has been provided by electron microscopy of intact, active photosystem II at 15-30 A resolution, and by electron crystallography on two-dimensional crystals of D1-D2-CP47 photosystem II fragments without water oxidizing activity at 8 A resolution. Here we describe the X-ray structure of photosystem II on the basis of crystals fully active in water oxidation. The structure shows how protein subunits and cofactors are spatially organized. The larger subunits are assigned and the locations and orientations of the cofactors are defined. We also provide new information on the position, size and shape of the manganese cluster, which catalyzes water oxidation.

1,847 citations


Journal ArticleDOI
TL;DR: In this paper, the production of nanoparticles on a laboratory scale is presented, special features such as increased saturation solubility and dissolution velocity are discussed, and special applications are highlighted, for example, mucoadhesive nanosuspensions for oral delivery and surface-modified drug nanoparticles for site-specific delivery to the brain.

1,349 citations


Book
01 Jan 2001
TL;DR: This study is based on data on a panel of households recruited as a random telephone sample of the U.S. population, each household in the sample--with or without prior Internet connection--was equipped with a WebTV® set-top box, with free Internet access and email accounts.
Abstract: [Editor's note: This study is based on data on a panel of households recruited as a random telephone sample of the U.S. population. In order to use the Internet for the purpose of efficient multi-channel data collection, each household in the sample--with or without prior Internet connection--was equipped with a WebTV® set-top box, with free Internet access and email accounts. The data for the study were collected in December 1999, from a national random sample of 4,113 individuals in 2,689 panel households. The margin of sampling error is about ±1.5% for results from the complete survey, and about ±2.5% for the subset of Internet users.]

768 citations


Journal ArticleDOI
TL;DR: Whether bromelain will gain wide acceptance as a drug that inhibits platelet aggregation, is antimetastatic and facilitates skin debridement, among other indications, will be determined by further clinical trials.
Abstract: Bromelain is a crude extract from the pineapple that contains, among other components, various closely related proteinases, demonstrating, in vitro and in vivo, antiedematous, antiinflammatory, antithrombotic and fibrinolytic activities. The active factors involved are biochemically characterized only in part. Due to its efficacy after oral administration, its safety and lack of undesired side effects, bromelain has earned growing acceptance and compliance among patients as a phytotherapeutical drug. A wide range of therapeutic benefits has been claimed for bromelain, such as reversible inhibition of platelet aggregation, angina pectoris, bronchitis, sinusitis, surgical traumas, thrombophlebitis, pyelonephritis and enhanced absorption of drugs, particularly of antibiotics. Biochemical experiments indicate that these pharmacological properties depend on the proteolytic activity only partly, suggesting the presence of nonprotein factors in bromelain. Recent results from preclinical and pharmacological studies recommend bromelain as an orally given drug for complementary tumor therapy: bromelain acts as an immunomodulator by raising the impaired immunocytotoxicity of monocytes against tumor cells from patients and by inducing the production of distinct cytokines such as tumor necrosis factor-α, interleukin (Il)-1β, Il-6, and Il-8. In a recent clinical study with mammary tumor patients, these findings could be partially confirmed. Especially promising are reports on animal experiments claiming an antimetastatic efficacy and inhibition of metastasis-associated platelet aggregation as well as inhibition of growth and invasiveness of tumor cells. Apparently, the antiinvasive activity does not depend on the proteolytic activity. This is also true for bromelain effects on the modulation of immune functions, its potential to eliminate burn debris and to accelerate wound healing. Whether bromelain will gain wide acceptance as a drug that inhibits platelet aggregation, is antimetastatic and facilitates skin debridement, among other indications, will be determined by further clinical trials. The claim that bromelain cannot be effective after oral administration is definitely refuted at this time.

591 citations


Journal ArticleDOI
TL;DR: Converging arguments from preclinical and clinical studies support the hypothesis that the loudness dependence of the auditory evoked N1/P2-response (LDAEP) is regulated by the level of central serotonergic neurotransmission.

555 citations


Journal ArticleDOI
19 Apr 2001-Nature
TL;DR: It is shown that honeybees can form ‘sameness’ and ‘difference’ concepts, and not only can bees learn specific objects and their physical parameters, but they can also master abstract inter-relationships, such as sameness and difference.
Abstract: Insects process and learn information flexibly to adapt to their environment. The honeybee Apis mellifera constitutes a traditional model for studying learning and memory at behavioural, cellular and molecular levels. Earlier studies focused on elementary associative and non-associative forms of learning determined by either olfactory conditioning of the proboscis extension reflex or the learning of visual stimuli in an operant context. However, research has indicated that bees are capable of cognitive performances that were thought to occur only in some vertebrate species. For example, honeybees can interpolate visual information, exhibit associative recall, categorize visual information and learn contextual information. Here we show that honeybees can form 'sameness' and 'difference' concepts. They learn to solve 'delayed matching-to-sample' tasks, in which they are required to respond to a matching stimulus, and 'delayed non-matching-to-sample' tasks, in which they are required to respond to a different stimulus; they can also transfer the learned rules to new stimuli of the same or a different sensory modality. Thus, not only can bees learn specific objects and their physical parameters, but they can also master abstract inter-relationships, such as sameness and difference.

545 citations


Journal ArticleDOI
TL;DR: It is found that phosphatidylinositol 3-phosphate (PI[3]P) accumulates greatly but transiently on the phagosomal membrane, and the possibility that PI(3)P production by VPS34 may be targeted during the maturation arrest induced by some intracellular parasites is raised.
Abstract: Phagosomes acquire their microbicidal properties by fusion with lysosomes. Products of phosphatidylinositol 3-kinase (PI 3-kinase) are required for phagosome formation, but their role in maturation is unknown. Using chimeric fluorescent proteins encoding tandem FYVE domains, we found that phosphatidylinositol 3-phosphate (PI[3]P) accumulates greatly but transiently on the phagosomal membrane. Unlike the 3'-phosphoinositides generated by class I PI 3-kinases which are evident in the nascent phagosomal cup, PI(3)P is only detectable after the phagosome has sealed. The class III PI 3-kinase VPS34 was found to be responsible for PI(3)P synthesis and essential for phagolysosome formation. In contrast, selective ablation of class I PI 3-kinase revealed that optimal phagocytosis, but not maturation, requires this type of enzyme. These results highlight the differential functional role of the two families of kinases, and raise the possibility that PI(3)P production by VPS34 may be targeted during the maturation arrest induced by some intracellular parasites.

529 citations


Journal ArticleDOI
TL;DR: Fantasy realization theory states that when people contrast their fantasies about a desired future with reflections on present reality, a necessity to act is induced that leads to the activation and use of relevant expectations.
Abstract: Fantasy realization theory states that when people contrast their fantasies about a desired future with reflections on present reality, a necessity to act is induced that leads to the activation and use of relevant expectations. Strong goal commitment arises in light of favorable expectations, and weak goal commitment arises in light of unfavorable expectations. To the contrary, when people only fantasize about a desired future or only reflect on present reality, expectancy-independent moderate goal commitment emerges. Four experiments pertaining to various life domains supported these hypotheses. Strength of goal commitment was assessed in cognitive (e.g., making plans), affective (e.g., felt attachment), and behavioral terms (e.g., effort expenditure, quality of performance). Implications for theories on goal setting and goal striving are discussed.

Journal ArticleDOI
TL;DR: The crystal structure analysis of the complex with tetracycline revealed the functionally important site responsible for the blockage of the A‐site and implies that the anti‐association activity of IF3 is due to its influence on the conformational dynamics of the small ribosomal subunit.
Abstract: The small ribosomal subunit is responsible for the decoding of genetic information and plays a key role in the initiation of protein synthesis. We analyzed by X-ray crystallography the structures of three different complexes of the small ribosomal subunit of Thermus thermophilus with the A-site inhibitor tetracycline, the universal initiation inhibitor edeine and the C-terminal domain of the translation initiation factor IF3. The crystal structure analysis of the complex with tetracycline revealed the functionally important site responsible for the blockage of the A-site. Five additional tetracycline sites resolve most of the controversial biochemical data on the location of tetracycline. The interaction of edeine with the small subunit indicates its role in inhibiting initiation and shows its involvement with P-site tRNA. The location of the C-terminal domain of IF3, at the solvent side of the platform, sheds light on the formation of the initiation complex, and implies that the anti-association activity of IF3 is due to its influence on the conformational dynamics of the small ribosomal subunit.

Proceedings Article
03 Jan 2001
TL;DR: This work detects upcoming finger movements in a natural keyboard typing condition and predicts their laterality in a pseudo-online simulation, and compares discriminative classifiers like Support Vector Machines (SVMs) and different variants of Fisher Discriminant that possess favorable regularization properties for dealing with high noise cases.
Abstract: Driven by the progress in the field of single-trial analysis of EEG, there is a growing interest in brain computer interfaces (BCIs), i.e., systems that enable human subjects to control a computer only by means of their brain signals. In a pseudo-online simulation our BCI detects upcoming finger movements in a natural keyboard typing condition and predicts their laterality. This can be done on average 100-230ms before the respective key is actually pressed, i.e., long before the onset of EMG. Our approach is appealing for its short response time and high classification accuracy (>96%) in a binary decision where no human training is involved. We compare discriminative classifiers like Support Vector Machines (SVMs) and different variants of Fisher Discriminant that possess favorable regularization properties for dealing with high noise cases (inter-trial variablity).

Journal ArticleDOI
TL;DR: In this paper, the X-ray structure of photosystem I at a resolution of 2.5 A O shows the location of the individual subunits and cofactors and provides new information on the protein-cofactor interactions.

Journal ArticleDOI
TL;DR: Bcl-2 overexpression abolished apoptosis triggered by both apoptotic stimuli, confirming the critical role of the Bax/B cl-2 ratio as a rheostat that determines the susceptibility to apoptosis in melanoma cells by regulating mitochondrial function.

Journal ArticleDOI
TL;DR: The honeybee is used as a useful model for the study of intermediate levels of complexity in cognitive functions and the search for their neural substrates and it is shown that behavioural complexity in the honeybee cannot be explained by independent functions of vertically arranged, domain-specific processing modules, but requires horizontal integration in a central state.

Journal ArticleDOI
TL;DR: Multiple examples are found where peptide X--H...pi interactions are functional in stabilization of helix termini, strand ends, strand edges, beta-bulges and regular turns, as well as in alpha-helices and beta-sheets.

Journal ArticleDOI
TL;DR: Data on associative learning and memory formation in honeybees is presented, emphasizing a comparative approach and believed that bees might be a useful model for studying cognitive faculties at a middle level of complexity.
Abstract: To determine general or species-specific properties in neural systems, it is necessary to use comparative data in evaluating experimental findings. Presented here are data on associative learning and memory formation in honeybees, emphasizing a comparative approach. We focus on four aspects: (1) the role of an identified neuron, VUMmx1, as a neural substrate of appetitive reinforcement; (2) the sequences of molecular events as they correlate with five forms of memory stages; (3) the localization of the memory traces following appetitive olfactory learning; and (4) the brief description of several forms of complex learning in bees (configuration in olfactory conditioning, categorization in visual feature learning, delayed matching-to-sample learning, and latent learning in navigation). VUMmx1 activity following the conditioned stimulus odor is sufficient to replace the unconditioned stimulus, and VUMmx1 changes its response properties during learning similarly to what is known from dopamine neurons in the basal ganglia of the mammalian brain. The transition from short- to mid- and long-term forms of memory can be related to specific activation of second messenger cascades (involving NOS, PKA, PKC, and PKM) resembling general features of neural plasticity at the cellular level. The particular time course of the various memory traces may be adapted to the behavioral context in which they are used; here, the foraging cycle of the bee. Memory traces for even such a simple form of learning as olfactory conditioning are multiple and distributed, involving first- and second-order sensory neuropils (antennal lobe and mushroom bodies), but with distinctly different properties. The wealth of complex forms of learning in the context of foraging indicates basic cognitive capacities based on rule extraction and context-dependent learning. It is believed that bees might be a useful model for studying cognitive faculties at a middle level of complexity. Learning and Memory in a Mini-Brain Neuroscience needs a multitude of model systems. Practical reasons favor the study of very few, probably <100 species, of the two million and more animal species for in-depth studies of brain mechanisms and the relationship between brain and behavior. Although this strategy of focusing on a rather small selection of potentially interesting and practically useful species has certainly been one of the reasons for neuroscience’s success, it carries two dangers: of interpreting species-specific solutions as general mechanisms, and of overlooking the richness of mechanistic implementations for solving similar environmental demands developed during evolution. We learn from similarities and differences when we compare species, and we only recognize general mechanisms when we discover them all over again. As long as we deal with basic molecular and cellular properties of neural functions we are rather safe in assuming widespread use across species, but sensory, motor, and cognitive functions of even low complexity may be strongly adapted to the species’ ecological niche, and thus reflect different solutions. Conversely, neural systems that effectively solve common demands in animal life may be conserved in phy

Journal ArticleDOI
TL;DR: Model calculations confirm that this manipulation of individual specially designed porphyrin-based molecules by scanning tunneling microscopy at low temperature realizes the principle of a conformational molecular switch.
Abstract: A detailed experimental and theoretical investigation of the processes involved in the manipulation of individual specially designed porphyrin-based molecules by scanning tunneling microscopy at low temperature is presented. On a stepped Cu(211) surface, the interaction between tip and molecule was used to locally modify in a reversible way the internal configuration of a single molecule, thus drastically changing the tunneling current passing through it. Model calculations confirm that this manipulation realizes the principle of a conformational molecular switch.

Journal Article
TL;DR: The autochthonous Lactobacillus and Bifidobacterium microflora in man will remain stable life-long, however, some successions may be caused by transient species derived from food or from the oral cavity, thus giving the impression of an altered microFLora.
Abstract: Lactobacillus and bifidobacterial cultures are increasingly used as probiotics in pharmaceuticals and in foods. The selection of strains is performed often for technological rather than for microecological reasons. Detailed reports about species and strains composition of these microorganisms in the intestinal microflora of man are rare. Our investigations were performed with samples originating from infants and adults, taken from faeces and from upper sections of the intestinal tract including mouth and stomach, and from caecum and colon. Post mortem cases as well as test subjects under physiological conditions were analyzed using an automatic capsule system sampling at defined times in different parts of the intestinal tract. The fate of selected strains after oral intake was studied, too. Furthermore, influences of the microflora originating from food were considered. The identification of autochthonous (indigenous) and allochthonous (transient) species could be achieved with descriptions of new species in the genera Lactobacillus and Bifidobacterium. L. gasseri and L. reuteri proved to be predominant autochthonous Lactobacillus species in infants as well as in adults. Both species were occasionally present even in the stomach. This was also the case with an anaerobic lactic acid bacterium, previously named Catenabacterium catenaforme, later classified as L. ruminis, a non-motile variant of this species. The bifidobacterial microflora differed in composition between infants and adults and in different stages of the host’s life. Up to 5 species or special strains of bifidobacteria could be present in different, individually fixed, combinations. Species typical for infants were B. bifidum, B. infantis, B. breve, and B. parvulorum. Typical for adults were 4 different variants of B. adolescentis. B. bifidum and B. longum could often be found in both groups, but in lower numbers. B. longum showed some oxygen tolerance whereas B. bifidum and B. adolescentis required strict anaerobic and fastidious conditions for cultivation. The autochthonous Lactobacillus and Bifidobacterium microflora in man will remain stable life-long. With lactobacilli, however, some successions may be caused by transient species derived from food or from the oral cavity, thus giving the impression of an altered microflora. Nevertheless L. gasseri, L. reuteri, L. ruminis, and to some degree, L. salivarius, may be present as autochthonous species all of the time. With bifidobacteria, a decreasing tendency in counts and in multiple composition in elderly people exists. Furthermore, this microflora is also influenced by consumption habits, which are probably caused by geographical circumstances.

Journal ArticleDOI
TL;DR: The presented approach is considered as a useful means to determine valid conditions for the analysis of prosthesis loading, bone modeling or remodeling processes around implants and fracture stability following internal fixation.

Journal ArticleDOI
TL;DR: In this paper, a density matrix technique is introduced as the theoretical tool providing a unified description of the processes which follow ultrafast laser excitation, including coherent exciton motion, vibrational coherences, exciton relaxation, and exciton localization.

Journal ArticleDOI
01 Nov 2001-Chest
TL;DR: Levels of circulating ET-1 might become a prognostic marker for patients with PPH and serve as a tool for the selection of patients who may benefit from treatment with ET-receptor antagonists.

Journal ArticleDOI
TL;DR: A portable activity monitoring system was developed and applied for the determination of frequency and duration of patient activities in their habitual environment and to compare the results to a clinical outcome score (Harris hip score).

Journal ArticleDOI
TL;DR: The domains characterized in this work provide for the rapid construction of artificial transcription factors, thereby greatly increasing the number of sequences and genes that can be targeted by DNA-binding proteins built from pre-defined zinc finger domains.

Journal ArticleDOI
TL;DR: It is suggested that CRB1 mutations are a frequent cause of LCA and are strongly associated with the development of Coats-like exudative vasculopathy in patients with RP.
Abstract: Mutations in the crumbs homologue 1 (CRB1) gene cause a specific form of retinitis pigmentosa (RP) that is designated "RP12" and is characterized by a preserved para-arteriolar retinal pigment epithelium (PPRPE) and by severe loss of vision at age <20 years. Because of the early onset of disease in patients who have RP with PPRPE, we considered CRB1 to be a good candidate gene for Leber congenital amaurosis (LCA). Mutations were detected in 7 (13%) of 52 patients with LCA from the Netherlands, Germany, and the United States. In addition, CRB1 mutations were detected in five of nine patients who had RP with Coats-like exudative vasculopathy, a relatively rare complication of RP that may progress to partial or total retinal detachment. Given that four of five patients had developed the complication in one eye and that not all siblings with RP have the complication, CRB1 mutations should be considered an important risk factor for the Coats-like reaction, although its development may require additional genetic or environmental factors. Although no clear-cut genotype-phenotype correlation could be established, patients with LCA, which is the most severe retinal dystrophy, carry null alleles more frequently than do patients with RP. Our findings suggest that CRB1 mutations are a frequent cause of LCA and are strongly associated with the development of Coats-like exudative vasculopathy in patients with RP.

Journal ArticleDOI
TL;DR: The health action process approach as discussed by the authors is explicitly based on the assumption that two distinct phases need to be studied longitudinally, one phase that leads to a behavioral intention and another phase leading to the actual behavior.
Abstract: Changing health-related behaviors requires two separate processes that involve motivation and volition, respectively. First, an intention to change is developed, in part on the basis of self-beliefs. Second, the change must be planned, initiated, and maintained, and relapses must be managed; self-regulation plays a critical role in these processes. Social-cognition models of health behavior change address these two processes. One such model, the health action process approach, is explicitly based on the assumption that two distinct phases need to be studied longitudinally, one phase that leads to a behavioral intention and another that leads to the actual behavior. Particular social-cognitive variables may play different roles in the two stages; perceived self-efficacy is the only predictor that seems to be equally important in the two phases.

Journal ArticleDOI
15 Sep 2001-Cancer
TL;DR: In this paper, actual evidence of the relationship between fatigue and impairment of physical performance in cancer patients and suggestions for new directions for research are discussed, as well as the importance of physical exercise programs in reducing the intensity of cancer-related fatigue.
Abstract: Cancer patients frequently suffer from fatigue and loss of physical performance. Several biologic, psychologic, and social factors have been suggested as explanations for the origins of fatigue in this context. In most cases, fatigue has a multifactorial genesis. However, recent studies suggest that fatigue may originate from alterations in the muscular energetic systems caused by cancer and its treatment. Furthermore, there is growing evidence that physical exercise programs help prevent the manifestation and reduce the intensity of cancer-related fatigue. In this article, actual evidence of the relationship between fatigue and impairment of physical performance in cancer patients and suggestions for new directions for research are discussed.

Journal ArticleDOI
TL;DR: The degree of plaque disruption (erosion, fissure, or ulceration) and the amount of stenosis caused by the disrupted plaque and the overlying mural thrombus are key factors for determining thrombogenicity at the local arterial site.
Abstract: Long-term treatment with potent antithrombotic drugs, such as tissue factor or factor Xa inhibitors, that effectively block thrombosis without causing bleeding complications could help reduce death...

Book ChapterDOI
01 Jan 2001
TL;DR: For instance, the authors pointed out that novelty and familiarity in features of the environment are important factors in the influence of stimuli that influence human behavior, and that novelty is correlated with familiarity.
Abstract: Nearly fifty years ago D. F. Berlyne (1950) wrote Psychology has so far had surprisingly little to say about stimuli which influence behavior simply because they are new. Stimuli which owe their potency to the fact that they are not new ... have given rise to the vast corpus of observations and generalization that go to make up learning theory. But the everyday activity of both men and animals seem [sic] to attest to the importance of novelty as well as familiarity in features of the environment.