julilili42/papers huggingface dataset:
Analysis of Historical Data Suggests Long-lasting Protective Effects of Smallpox Vaccination
2003-10-15

More than half of the US population has received the smallpox vaccine, but it is unknown what fraction is still protected against infection and disease. Residual protection and age-dependent case-fatality ratios have therefore been widely neglected in the current bioterrorism debate. The author analyzed 1902-1903 data from Liverpool, United Kingdom, and from reintroductions of the disease to Europe in 1950-1971 to estimate to what degree vaccinated cases were protected against developing severe or fatal disease and how quickly this protection waned over time. Protection against severe and fatal disease was lost at the rate of 1.41% per year, corresponding to a half-life of 49.2 years (95% confidence interval: 42.0, 57.3), and protection against fatal disease alone declined 0.363% per year. Thus, even 70 years after primary vaccination, 77.6% of cases were still protected (95% confidence interval: 66.6, 85.4). Protection against severe disease should therefore extend for many decades after a single vaccination, and protection against death from smallpox may even be lifelong for the majority of vaccinees. This protection should greatly reduce the number of severe and fatal cases of disease expected in a bioterrorist attack, but residual protection may also increase the risk that some previously vaccinated cases who develop mild disease may remain unrecognized longer, while moving around freely and disseminating the infection.
Charge carrier photogeneration in oligo(phenylenevinylene) thin films: A quantitative study
2003-10-15

We analyze the generation and recombination of charged states in oligo(phenylenevinylene)s at high photoexcitation densities, using femtosecond pump-probe spectroscopy as a direct probe for the time-dependent density of photogenerated singlet, triplet, and doublet states. Pairs of charged states are formed during the exciting laser pulse, partly by a two-photon process. Geminate recombination of these pairs is found in the first ps after formation, after which a nongeminate dispersive mechanism prevails. The application of high electric field strengths opens up an additional channel for charge carrier formation, involving field-induced electron transfer between two singlet excitons. This process is competing with bimolecular singlet exciton annihilation. Field-induced formation of triplet states is governed by nongeminate recombination of field-induced charged states. We give values for cross sections of the photogenerated species, the efficiency of field-induced charge carrier photogeneration and for the early charge carrier mobility. © 2003 The American Physical Society.
Ageing, autoimmunity and arthritis: Perturbations of TCR signal transduction pathways with ageing – a biochemical paradigm for the ageing immune system
2003-10-16

It is widely accepted that cell-mediated immune functions decline with age, rendering an individual more susceptible to infection and possibly cancer, as well as to age-associated autoimmune diseases. The exact causes of T-cell functional decline are not known. One possible cause could be the development of defects in the transduction of mitogenic signals following TCR stimulation. This T-cell hyporesponsiveness due to defects of signalling through the TCR either from healthy elderly subjects or from individuals with autoimmune diseases such as rheumatoid arthritis or systemic lupus erythematosus results in an impaired ability to mount efficient immune responses and to maintain responsiveness to foreign antigens. This implies that a high proportion of autoreactive T cells might accumulate either intrathymically or in the periphery. T-cell anergy and differential TCR signalling could thus also be key players in the disruption of tolerance and the onset of autoimmune diseases. The increasing number of the elderly may lead to an increase of clinically important autoimmune diseases. We will review the signal transduction changes through the TCR-CD3 complex in T lymphocytes from healthy elderly subjects, which result in a modification of the activation of transcription factors involved in IL-2 gene expression leading to decreased IL-2 production. The putative contribution of altered T-cell signalling with ageing in the development of autoimmune diseases will be also discussed.
An unusual amide synthetase (CouL) from the coumermycin A1 biosynthetic gene cluster from Streptomyces rishiriensis DSM 40489
2003-10-16

The aminocoumarin antibiotic coumermycin A 1 produced by Streptomyces rishiriensis DSM 40489 contains two amide bonds. The biosynthetic gene cluster of coumermycin contains a putative amide synthetase gene, couL , encoding a protein of 529 amino acids. CouL was overexpressed as hexahistidine fusion protein in Escherichia coli and purified by metal affinity chromatography, resulting in a nearly homogenous protein. CouL catalysed the formation of both amide bonds of coumermycin A 1 , i.e. between the central 3‐methylpyrrole‐2,4‐dicarboxylic acid and two aminocoumarin moieties. Gel exclusion chromatography showed that the enzyme is active as a monomer. The activity was strictly dependent on the presence of ATP and Mn 2+ or Mg 2+ . The apparent K m values were determined as 26 μ m for the 3‐methylpyrrole‐2,4‐dicarboxylic acid and 44 μ m for the aminocoumarin moiety, respectively. Several analogues of the pyrrole dicarboxylic acid were accepted as substrates. In contrast, pyridine carboxylic acids were not accepted. 3‐Dimethylallyl‐4‐hydroxybenzoic acid, the acyl component in novobiocin biosynthesis, was well accepted, despite its structural difference from the genuine acyl substrate of CouL.
Generating Data for Databases—The Peptide Repertoire of HLA Molecules
2003-10-16

During the past few years, a huge amount of information about HLA-presented peptides has been compiled: several thousand naturally processed ligands of such cell surface receptors are already known. Nevertheless, our knowledge covers only a minute proportion of the total peptide repertoire. The overall amount of different peptides presented by one given HLA class I molecule lies between 1000 and 10000 individual sequences per cell. There is, however, no HLA molecule of which more than 100 ligands have been published so far. The situation is further complicated by the fact that different cells present different sets of peptides by the same HLA molecules, a feature that provides great hope for immunotherapy. We have been analysing HLA-presented peptides for many years for three reasons. First, the basic rules of peptide presentation (the 'peptide motifs') had to be established. Second, the listing of individual peptides presented by HLA molecules is steadily continuing, although a comprehensive catalogue of all possible HLA-presented peptides is utopical in our days. Third, quantitative differences in the presentation of individual HLA ligands provide information about the dynamic state of the host cells. Comprehensive information about HLA-presented peptides enables accurate epitope prediction and provides a basis for diagnostic assessment and therapeutic intervention.
The calcium sensor CBL1 integrates plant responses to abiotic stresses
2003-10-17

Summary Calcium ions represent both an integrative signal and an important convergence point of many disparate signaling pathways. Calcium‐binding proteins, like calcineurin B‐like (CBL) proteins, have been implicated as important relays in calcium signaling. Here, we report the in vivo study of CBL1 function in Arabidopsis . Analyses of loss‐of‐function as well as CBL1 ‐overexpressing lines indicate a crucial function of this calcium sensor protein in abiotic stress responses. Mutation of CBL1 impairs plant responses to drought and salt stresses and affects gene expression of cold‐regulated genes, but does not affect abscisic acid (ABA) responsiveness. Conversely, overexpression of CBL1 reduces transpirational water loss and induces the expression of early stress‐responsive transcription factors and stress adaptation genes in non‐stressed plants. Together, our data indicate that the calcium sensor protein CBL1 may constitute an integrative node in plant responses to abiotic stimuli and contributes to the regulation of early stress‐related transcription factors of the C‐Repeat‐Binding Factor/dehydration‐responsive element (CBF/DREB) type.
Synthesis, Characterization, and Evaluation of Divinylbenzene-Coated Spherical Nonporous Silica
2003-10-17

Monodisperse nonporous silica particles were coated with different amounts of a divinylbenzene-based polymer resulting in a new class of reversed-phase high-performance liquid chromatographic material. An optimization of the polymer layer, with respect to the thickness, was performed to obtain optimal surface properties of the chromatographic sorbent. The materials were characterized using solid-state 13C CP/MAS NMR spectroscopy, thermogravimetry analysis, BET surface area measurements, scanning electron microscopy, and transmission electron microscopy. The application of the new materials in reversed-phase HPLC revealed extremely short separation times while maintaining a high chromatographic resolution.
Development of an MHC-class I peptide selection assay combining nanoparticle technology and matrix-assisted laser desorption/ionisation mass spectrometry
2003-10-18

Human leukocyte antigen (HLA)-bound peptides are central for recognition of infected/transformed cells by T cells, and have formed the basis for many immunotherapy strategies. Epitopes from a given protein sequence (e.g. from viral proteins or oncoproteins) can be predicted by algorithms, as individual HLA receptors bind peptides through defined binding motifs. Peptides with the highest predicted binding score are then normally tested for their binding ability in binding assays. However, with the assays already established, only one peptide can be tested for binding per assay. This is certainly not a reflection of the in vivo situation, where several peptides generated via the major histocompatability complex (MHC)-class I processing pathway compete for HLA-receptor binding. Here, we describe the development of a method that can mimic the competition between multiple peptides for binding to a single HLA receptor molecule. We used silica nanoparticles with immobilised HLA-A2 complexes to screen HLA-A2 binder-peptides out of a known peptide mixture. The washed beads were analysed for selectively bound peptides by matrix-assisted laser desorption/ionisation (MALDI) mass spectrometry. The advantage of the system is that the bound peptides can be unambiguously identified without any prior modification (e.g. radioactive or fluorescence labelling), even from complex peptide mixtures.
Anti‐tumor immune responses and tumor regression induced with mimotopes of a tumor‐associated T cell epitope
2003-10-20

Abstract Mimotopes provide an alternative to natural T cell epitopes for cancer immune therapy, as they can recruit and stimulate T cell repertoires that deviate from the repertoires engaged with the tumor and exposed to disease‐related immune suppression. Here, mimotopes of a shared tumor‐associated T cell epitope in cutaneous lymphoma were tested for their capacities to induce clinical and immunological responses in cancer patients. The mimotope sequences had been determined by a combinatorial peptide library approach without knowledge of the corresponding natural tumor‐associated antigen. Vaccination with these mimotopes together with helper T cell‐inducing antigens led to complete tumor remission in the two patients tested. After each booster vaccination, enhanced frequencies of mimotope‐specific CD8 + T cells were detected in the peripheral blood of the patients, and the CTL proved to be cytotoxic and tumoricidal when tested in vitro . These data provide a first indication of clinical efficacy of mimotopes in cancer patients.
Four policies to reduce HIV transmission through unsterile health care
2003-10-21

Residents of many developing countries face risks for themselves and their families to contract HIV and other bloodborne pathogens during unsterile health care. Helping people to understand and reduce these risks enlists their assistance to control the HIV/AIDS epidemic. To reduce HIV transmission through health care, we recommend four policies that international, foreign, and local public and private organizations can adopt and begin to implement even with little or no additional funds: (1) Educate the public about risks to contract HIV through unsterile health care. (2) Promote transparent practices for injections and other procedures that allow patients to see and know that care is safe (e.g., taking a new auto-disable syringe out of a sealed package and taking injecta from a single-dose vial). (3) Promote safe health care practices equally for clients and staff. (4) Establish a zero-tolerance policy for iatrogenic HIV infections, with publicly reported monitoring and investigations.
A Whole Earth Telescope campaign on the pulsating subdwarf B binary system PG 1336−018 (NY Vir)
2003-10-23

We present results from a multisite (‘Whole Earth Telescope’) photometric campaign on PG 1336−018, the close eclipsing binary system containing a pulsating subdwarf B (sdB) star. The main part of the campaign (1999 April) resulted in ∼172 h of observations, representing a coverage of about 47 per cent, and additional data were obtained outside the core campaign. Periodogram analysis shows that the light variations are dominated by three frequencies near 5757, 5585 and 5369 μHz (∼174, 179 and 186 s, respectively), although many frequencies are present, particularly in the range 5000–6000 μHz (∼200–170 s). We identify, with some confidence, 28 frequencies down to a semi-amplitude of 0.0005 in fractional intensity (equivalent to about 0.5 mmag). It is clear that the pulsation frequencies of PG 1336−018 have changed substantially since the 1996 discovery observations were made, and that amplitude changes occur, at least in the dominant three frequencies, on relatively short time-scales (of the order of a day). On the assumption that the pulsating star is phase-locked in the binary system, we have searched for rotational splitting of frequencies near the orbital and half of the orbital period, but the results are confused by aliasing at those frequencies (due to the data gaps caused by the eclipses). A preliminary model qualitatively matches the distribution of frequencies in PG 1336−018, with some good individual correspondences, but cannot be considered adequate because geometric cancellation should hide some of the modes which are apparently detected. Analysis of the pulsations during eclipse recovers three of the strongest modes, but the limited eclipse data — which can, at best, be only about 9 per cent of the total — do not allow mode identification at this stage. Simulations indicate that an overall coverage of about 80 per cent would be required for this to be viable. An attempt was made to determine phase shifts in the pulsation frequencies as a way of directly measuring the size of the binary orbit, but the uncertainties in the method are comparable to the light travel time across the orbit (probably less than a second).
Antibodies to Plasmodium falciparum Rifin Proteins Are Associated with Rapid Parasite Clearance and Asymptomatic Infections
2003-10-24

ABSTRACT Plasmodium falciparum rifin proteins, belonging to the largest known family of variable infected-erythrocyte surface-expressed proteins encoded by rif genes, were recently shown to be capable of inducing a strong immune response in P. falciparum -infected adults living in an area in Gabon where malaria is endemic. In the present study, the levels of antirifin antibodies were analyzed in serum obtained from 60 children from the same area who were admitted to hospital and diagnosed with severe malaria. High antirifin antibody concentrations in these individuals correlated significantly with their capacity to rapidly clear their parasites from the circulation after the start of chemotherapy. A doubling of antirifin antibody concentrations reduced the clearance time by 5 h (95% confidence interval, 4.1 to 6.9 h). In the same group of children, who were followed up for 2 years, antirifin antibody levels did not correlate with a reduced rate of reinfection or with a delay in the time to the first reinfection. However, the initial antirifin antibody levels were sustained over the study period. The likelihood that these antibodies could confer a certain degree of protection against malaria is supported by our findings of statistically higher levels of antirifin antibodies to all four rifin proteins in a group of 42 asymptomatic parasitemic children.
In Vitro Activity and Interaction of Clindamycin Combined with Dihydroartemisinin against Plasmodium falciparum
2003-10-24

ABSTRACT Combination regimens are considered a valuable tool for the fight against drug-resistant falciparum malaria. This study was conducted to evaluate the antimalarial potential of clindamycin in combination with dihydroartemisinin in continuously cultured and in freshly isolated Plasmodium falciparum parasites, measuring the inhibition of Plasmodium falciparum histidine-rich protein II synthesis. Interaction analysis revealed a synergistic or additive mode of interaction at various concentration ratios in all continuously cultured parasites at the 50% effective concentration (EC 50 ) level. Antagonism was not found for any of the culture-adapted parasites. In fresh P. falciparum isolates, a fixed clindamycin-dihydroartemisinin combination exhibited additive activity at the EC 50 and EC 90 levels. The drug mixture showed no significant activity correlation to other commonly used antimalarials. The clindamycin-dihydroartemisinin combination appears to be a promising candidate for clinical investigation.
Superconducting Quantum interference devices: State-of-the-art and applications
2003-10-24

Superconducting quantum interference devices (SQUIDs) are sensitive detectors of magnetic flux. A SQUID consists of a superconducting loop interrupted by either one or two Josephson junctions for the RF or dc SQUID, respectively. Low transition temperature (T/sub c/) SQUIDs are fabricated from thin films of niobium. Immersed in liquid helium at 4.2 K, their flux noise is typically 10/sup -6//spl Phi//sub 0/ Hz/sup -1/2/, where /spl Phi//sub 0//spl equiv/h/2e is the flux quantum. High-T/sub c/ SQUIDs are fabricated from thin films of YBa/sub 2/Cu/sub 3/O/sub 7-x/, and are generally operated in liquid nitrogen at 77 K. Inductively coupled to an appropriate input circuit, SQUIDs measure a variety of physical quantities, including magnetic field, magnetic field gradient, voltage, and magnetic susceptibility. Systems are available for detecting magnetic signals from the brain, measuring the magnetic susceptibility of materials and geophysical core samples, magnetocardiography and nondestructive evaluation. SQUID microscopes detect magnetic nanoparticles attached to pathogens in an immunoassay technique and locate faults in semiconductor packages. A SQUID amplifier with an integrated resonant microstrip is within a factor of two of the quantum limit at 0.5 GHz and will be used in a search for axions. High-resolution magnetic resonance images are obtained at frequencies of a few kilohertz with a SQUID-based detector.
Ca2+-Mobilization and Cell Contraction after Muscarinic Cholinergic Stimulation of the Chick Embryo Lens
2003-10-24

The localization of ChAT in the differentiating fibers of the lens indicates that acetylcholine is synthesized during differentiation and modulates morphogenesis and elongation of mAChR-positive progenitor cells in the equatorial zone. The carbachol-induced contraction indicates that the embryonic muscarinic system may be involved in the regulation of cellular movements.
Protein microarrays: Promising tools for proteomic research
2003-10-27

Abstract Miniaturized and parallelized ligand binding assays are of great interest in postgenomic research because microarray technology allows the simultaneous determination of a large number of parameters from a minute amount of sample within a single experiment. Assay systems based on this technology are used for the identification and quantification of proteins as well as for the study of protein interactions. Protein affinity assays have been implemented that allow the analysis of interactions between proteins with other proteins, peptides, low molecular weight compounds, oligosaccharides or DNA. Microarray technology is an emerging technology used in global analytical approaches and has a considerable impact on proteomic research.
IBIS: The Imager on-board INTEGRAL
2003-10-28

The IBIS telescope is the high angular resolution gamma-ray imager on-board the INTEGRAL Observatory, successfully launched from Baikonur (Kazakhstan) the 17th of October 2002. This medium size ESA project, planned for a 2 year mission with possible extension to 5, is devoted to the observation of the gamma-ray sky in the energy range from 3 keV to 10 MeV (Winkler 2001). The IBIS imaging system is based on two independent solid state detector arrays optimised for low ( 15-1000 keV) and high ( 0.175-10.0 MeV) energies surrounded by an active VETO System. This high efficiency shield is essential to minimise the background induced by high energy particles in the highly excentric out of van Allen belt orbit. A Tungsten Coded Aperture Mask, 16 mm thick and ~1 squared meter in dimension is the imaging device. The IBIS telescope will serve the scientific community at large providing a unique combination of unprecedented high energy wide field imaging capability coupled with broad band spectroscopy and high resolution timing over the energy range from X to gamma rays. To date the IBIS telescope is working nominally in orbit since more than 9 month.
Three-periodic nets and tilings: semiregular nets
2003-10-28

Three-periodic semiregular nets are defined as those with just one kind of vertex and one kind of edge, but excluding the five regular and one quasiregular nets described earlier. Fourteen of these and their natural tilings are described and their importance in crystal chemistry is indicated.
Phase II trial of intralesional therapy with interleukin-2 in soft-tissue melanoma metastases
2003-10-28

The objective of the present study was to validate the use of intralesional injection of interleukin-2 (IL-2) in patients with skin and soft-tissue melanoma metastases. A total of 24 patients with AJCC stage III or IV melanoma and single or multiple skin and soft-tissue metastases were included. Interleukin-2 injections were administered intralesionally into the total number of cutaneous and soft-tissue metastases accessible from the skin, 2-3 times weekly, over 1-57 weeks. Single doses varied from 0.6 to 6 x 10(6) IU, depending on lesion size. The clinical response was monitored by sonography and confirmed by histopathology; response evaluation was confined to the intralesionally treated tumours. Complete response (CR) of the treated metastases was achieved in 15 patients (62.5%), the longest remission lasting 38 months to date. In five patients, partial response (PR) was achieved (21%) and in another three patients, progressive disease was observed (one patient not assessable). A total of 245 metastases were treated with CR in 209 (85%), and PR in 21 (6%). The therapy was generally well tolerated; the observed adverse events were mainly of grade 1-2 severity. Immunohistochemical studies showed the tumour cells undergoing apoptosis and revealed a mixed character of the inflammatory infiltrate. The unusual high CR rate in metastatic melanoma of 62.5% and the limited toxicity suggest that treatment of skin and soft-tissue melanoma metastases with intralesional injection of IL-2 may be a safe and effective alternative to conventional therapies. The optimal dosage and duration of this therapy still remain to be defined in larger prospective multicentre trials.