gebhart/patrepeval huggingface dataset:
Therapy of established tumour with a hybrid cellular vaccine generated by using granulocyte–macrophage colony‐stimulating factor genetically modified dendritic cells (1999)

Dendritic cells (DCs) are the most powerful of all antigen-presenting cells and play a critical role in the induction of primary immune responses. DC-based vaccination represents a potentially powerful strategy for cancer immunotherapy. In this study, a new approach for a DC-based melanoma vaccine was described. Splenic DCs from C57BL/6 mice were fused with B16 melanoma cells, and the resultant B16/DC hybrid cells expressed major histocompatibility complex (MHC) molecules - B7 as well as the B16 tumour marker M562 - which were enriched by Ia-mediated positive selection with a MiniMACS column. The fusion rates were 12.7-26.8%. To generate hybrid tumour vaccines with potentially greater potent therapeutic efficacy, we genetically engineered DCs with granulocyte-macrophage colony-stimulating factor (GM-CSF) prior to cell fusion. Recombinant adenovirus vector was used to mediate gene transfer into DCs with high efficiency and DCs expressed GM-CSF at 96-138 ng/105 cells/ml 24 hr after GM-CSF gene transfer. GM-CSF gene-modified DCs (DC.GM) exhibited higher expression of B7 and co-stimulatory capacity in mixed lymphocyte reaction (MLR). Fusion of DC.GM with B16 cells generated B16/DC.GM hybrid cells secreting GM-CSF at 59-63 ng/105 cells/ml. Immunization of C57BL/6 mice with the B16/DC hybrid vaccine elicited a specific cytotoxic T-lymphocyte (CTL) response and protected the immunized mice from B16 tumour challenge, reduced pulmonary metastases and extended the survival of B16 tumour-bearing mice. The B16/DC.GM hybrid vaccine was able to induce a CTL response and protective immunity more potently and tended to be therapeutically more efficacious than the B16/DC vaccine. In vivo depletion of T-cell subsets demonstrated that both CD8+ and CD4+ T cells were essential for the therapeutic effects of B16/DC and B16/DC.GM hybrid vaccines. Additionally, other non-specific effector cells may also contribute to tumour rejection induced by the B16/DC.GM hybrid vaccine. These data indicate that a DC-based hybrid tumour vaccine may be an attractive strategy for cancer immunotherapy, and that GM-CSF gene-modified DCs may lead to the generation of hybrid vaccines with potentially increased therapeutic efficacy.
Polydextrose functional fibre (2011)

Polydextrose (PDX) is a highly branched, randomly bonded glucose polymer which is not digested in the upper gastrointestinal tract, but is slowly fermented throughout the colon. It has been widely acknowledged as a soluble fibre, and human clinical, animal and in vitro studies have all demonstrated physiological effects associated with this feature. These effects include improving gut health, reducing glycaemic impact and inducing satiety (1–3). The high tolerance and technological properties of PDX allow the development of food products with a variety of nutritional improvements without compromising taste and texture profile.
Type I interferon signaling is required for activation of the inflammasome during Francisella infection (2007)

Francisella tularensis is a pathogenic bacterium whose virulence is linked to its ability to replicate within the host cell cytosol. Entry into the macrophage cytosol activates a host-protective multimolecular complex called the inflammasome to release the proinflammatory cytokines interleukin (IL)-1beta and -18 and trigger caspase-1-dependent cell death. In this study, we show that cytosolic F. tularensis subspecies novicida (F. novicida) induces a type I interferon (IFN) response that is essential for caspase-1 activation, inflammasome-mediated cell death, and release of IL-1beta and -18. Extensive type I IFN-dependent cell death resulting in macrophage depletion occurs in vivo during F. novicida infection. Type I IFN is also necessary for inflammasome activation in response to cytosolic Listeria monocytogenes but not vacuole-localized Salmonella enterica serovar Typhimurium or extracellular adenosine triphosphate. These results show the specific connection between type I IFN signaling and inflammasome activation, which are two sequential events triggered by the recognition of cytosolic bacteria. To our knowledge, this is the first example of the positive regulation of inflammasome activation. This connection underscores the importance of the cytosolic recognition of pathogens and highlights how multiple innate immunity pathways interact before commitment to critical host responses.
A Brief Overview and History of Temporary Fillers: Evolution, Advantages, and Limitations (2007)

Facial soft-tissue augmentation by injection has become increasingly popular as a minimally invasive option for patients seeking cosmetic facial enhancement. Surgical rejuvenation procedures of the face often relate to a less than comprehensive solution to many of the changes that occur with age. Indeed, the surgical "lift," while providing the opportunity for soft-tissue repositioning, often fails to provide volumetric restoration to the face that is lost with aging. Appreciating the necessity of replacing depleted soft tissue has allowed for a more comprehensive approach to total facial rejuvenation. Hundreds of filling agents are available worldwide, and the enormity of options has led to confusion about which agents work best, where, and why. The vast array of available soft-tissue filling agents can be distilled into two simple categories: nonpermanent and permanent. In this article, the authors mostly limit their discussion, consistent with the mission of this supplement, to the evolution of nonpermanent filling agents, providing a rationale for their emergence and their individual use.
Adoptive T‐cell transfer in cancer immunotherapy (2006)

Adoptive T-cell therapy has definite clinical benefit in relapsed leukaemia after allogeneic transplant and in Epstein-Barr virus-associated post-transplant lymphoproliferative disease. However, the majority of tumour targets are weakly immunogenic self-antigens and success has been limited in part by inadequate persistence and expansion of transferred T cells and by tumour-evasion strategies. Adoptive immunotherapy presents the opportunity to activate, expand and genetically modify T cells outside the tolerising environment of the host and a number of strategies to optimize the cellular product, including gene modification and modulation of the host environment, in particular by lymphodepletion, have been developed.
Cloning and Functional Characterization of a Potential-sensitive, Polyspecific Organic Cation Transporter (OCT3) Most Abundantly Expressed in Placenta (1998)

We have isolated a cDNA from rat placenta which, when expressed heterologously, mediates the transport of a wide spectrum of organic cations. The cDNA codes for a protein of 551 amino acids containing 12 putative transmembrane domains. Northern blot analysis indicates that this transporter is expressed most abundantly in the placenta and moderately in the intestine, heart, and brain. The expression is comparatively low in the kidney and lung and is undetectable in the liver. This transporter is distinct from the previously cloned organic cation transporters (OCT1, OCT2, NKT, NLT, RST, and OCTN1). When expressed in HeLa cells, the cDNA induces the transport of tetraethylammonium and guanidine. Competition experiments indicate that this transport process recognizes a large number of organic cations, including the neurotoxin 1-methyl-4-phenylpyridinium, as substrates. The cDNA-induced transport is markedly influenced by extracellular pH. However, when expressed in Xenopus laevis oocytes, the cDNA-induced transport is electrogenic, associated with the transfer of positive charge into the oocytes. Under voltage clamp conditions, tetraethylammonium evokes inward currents that are concentration- and potential-dependent. This potential-sensitive organic cation transporter, designated as OCT3, represents a new member of the OCT gene family.
Definition of an Unexpected Ligand Recognition Motif for αvβ6 Integrin (1999)

Integrin interactions with extracellular matrix proteins are mediated by brief oligopeptide recognition sequences, and synthetic peptides containing such sequences can inhibit integrin binding to the matrix. The RGD peptide motif is recognized by many integrins including alphav beta6, a specific receptor for fibronectin thought to support epithelial cell proliferation during wound healing and carcinoma progression. We report here the discovery of an unexpected non-RGD recognition motif for integrin alphav beta6. We compared the recognition profiles of recombinant alphav beta6 and alphav beta3 integrins by using phage display screening employing 7-mer and 12-mer peptide libraries. As predicted, phages binding strongly to alphav beta3 contained ubiquitous RGD sequences. However, on alphav beta6, in addition to RGD- containing phages, one-quarter of the population from the 12-mer library contained the distinctive consensus motif DLXXL. A synthetic DLXXL peptide, RTDLDSLRTYTL, selected from the phage sequences (clone-1) was a selective inhibitor of RGD-dependent ligand binding to alphav beta6 in isolated receptor assays (IC50 = 20 nM), and in cell adhesion assays (IC50 = 50 microM). DLXXL peptides were highly specific inhibitors of alphav beta6-fibronectin interaction as synthetic scrambled or reversed DLXXL peptides were inactive. NH2- and COOH-terminal modifications of the flanking amino acids suggested that the preceding two and a single trailing amino acid were also involved in interaction with alphav beta6. The DLXXL sequence is present in several matrix components and in the beta chain of many integrins. Although there is as yet no precise biological role known for DLXXL, it is clearly a specific inhibitory sequence for integrin alphav beta6 which has been unrecognized previously.
Arabidopsis Mutants Deficient in Diacylglycerol Acyltransferase Display Increased Sensitivity to Abscisic Acid, Sugars, and Osmotic Stress during Germination and Seedling Development (2002)

Arabidopsis seeds store triacylglycerol (TAG) as the major carbon reserve, which is used to support postgerminative seedling growth. Diacylglycerol acyltransferase (DGAT) catalyzes the final step in TAG synthesis, and two isoforms of DGAT have previously been identified in Arabidopsis. It has been shown that DGAT1 plays an important role in seed development because Arabidopsis with mutations at the TAG1 locus accumulate less seed oil. There is also evidence showing that DGAT1 is active after seed germination. The aim of this study is to investigate the effect of mutations of DGAT1 on postembryonic development in Arabidopsis. We carried out detailed analyses of two tag1 mutants in different ecotypic backgrounds of Arabidopsis. Results show that during germination and seedling growth, seed storage TAG degradation was not affected in the tag1 mutants. However, sugar content of the mutant seedlings is altered, and activities of the hexokinases are significantly increased in the tag1 mutant seedlings. The tag1 mutants are also more sensitive to abscisic acid, glucose, and osmotic strength of the medium in germination and seedling growth.
Dream Nanomachines (2005)

Abstract Locomotion on the nanoscale through a fluid environment is one of the grand challenges confronting nanoscience today. The vision is to synthesize, probe, understand, and utilize a new class of motors made from nanoscale building blocks that derive on‐board or off‐board power from in‐situ chemical reactions. The generated mechanical work allows these motors to move through a fluid phase while simultaneously or sequentially performing a task or series of tasks. Such tiny machines, individually or assembled into designed architectures, might someday transport medicine in the human body, conduct operations in cells, move cargo around microfluidic chips, manage light beams, agitate liquids close to electrode surfaces, and search for and destroy toxic organic molecules in polluted water streams. Are these just “ nanomachine dreams ”, or “ dream nanomachines ”? Some very recent exciting developments suggest that a world of amazing chemically powered nanomachines will be the way the story unfolds in the not‐too‐distant future!
Natural antioxidants in milk and dairy products (2017)

Milk antioxidants, both lipophilic (conjugated linoleic acid, α‐tocopherol, β‐carotene, vitamins A and D 3 , coenzyme Q 10 , phospholipids) and hydrophilic antioxidants (proteins, peptides, vitamins, minerals and trace elements) play a key role in maintaining pro‐oxidant and antioxidant homeostasis in the human body. Lipophilic antioxidants are characterised by high thermal stability and they are active in all dairy products. Lipophilic and hydrophilic antioxidants interact in the process of deactivating reactive oxygen species and the final products of lipid peroxidation. A negative correlation between milk consumption and the incidence of diet‐dependent diseases confirms that the consumption of milk and dairy products delivers health benefits.
Circadian rhythms of melatonin, cortisol and prolactin in patients with obsessive‐compulsive disorder (1994)

Plasma melatonin, cortisol and prolactin (PRL) levels were measured over a 24-h period in 13 drug-free patients with obsessive-compulsive disorder and in matched healthy subjects. The circadian profiles of melatonin and PRL were altered in patients; the circadian rhythm of cortisol was preserved, although at a higher level compared with normal controls. These changes were significantly related to the severity of the obsessive-compulsive symptoms. Further studies need to clarify the state- or trait-dependent character of these abnormalities.
Regulation of EGF receptor expression and function (1990)

From the results of these studies of the activities of the various EGF receptor mutants we were able to disassociate the ability of EGF to increase intracellular calcium from its ability to induce genes and to cause morphological transformation and growth. These results lead us to the following concept. The kinase domain has a C-terminal border at about residue 957. The remainder of the C-terminus is regulatory. The 164 amino acids from residue 1022 to 1186 constitute an inhibitory region for the kinase. It contributes to ligand-induced internalization because this is reduced in a mutant receptor truncated to residue 1052. Proximally within the C-terminus kinase inhibitory domain is a domain that is required for endocytosis and for raising intracellular calcium that we call the calcium internalization (CAIN) domain. In summary, we have found that the kinase activity of the EGF receptor is required for its function even when all of the self-phosphorylation sites have been removed. The EGF receptor has several distinct cytoplasmic domains that are important for its activity to regulate gene expression, DNA synthesis, and the intracellular calcium level. Biological signaling occurs from the cell surface via essential protein tyrosine kinase activity with ligand-induced internalization serving to abbrogate the biological signal.
Characteristics of human T-cell clones from BCG and killedM. lepraevaccinated subjects and tuberculosis patients (1986)

A total of 121 human T-cell clones from 9 BCG vaccinated healthy subjects , 42 T-cell clones from 6 normal volunteers vaccinated with killed M. leprae and 52 T-cell clones from 4 tuber culosis patients were raised from peripheral blood mononuclear cells CPBMC). Irrespective of the group of subjects, all the proliferating clones were CD4+ CD8-. Some clones were specific to the antigens against which they were raised and others were limited to broadly crossreactive in proliferative assays. Antigen specificity of 3 M. leprae specific T-cell clones tested, was also manitained in lymphokine and cytotoxicity assays. Responses of the clones to BCG and M. tuberculosis H37Rv parallelled closely. Although, 68 % and 63 % of M. lep rae raised T-cell clones responded to BCG and M. tuberculosis, respectively, only 9 % BCG raised T-cell clones and 23 % M. tuberculosis raised T-cell clones responded to M. leprae. Twenty four T-cell clones from BCG vaccinated subjects, 22 T-cell clones from M. leprae vaccinated volunteers and all the 52 T-cell clones from tuberculosis patients were tested for their reactivity to recombinant antigens of M. leprae and M. tuberculosis identified by mono clonal antibodies. Five specific clones from 2 M. leprae vaccinated subjects recognized an epitope on the M. leprae 1 8K protein, and one nonspecific clone from a third individual reacted to both the M. leprae and M. tuberculosis 65K proteins. From tuberculosis patients , one specific clone responded to the M. tuberculosis 65K protein while another limited cross reactive clone proliferated to the M. tuberculosis 19K protein. None of the 24 BCG induced T-cell clones responded to the recombinant antigens.
Gene Amplification in Bacillus subtilis (1984)

A strain of Bacillus subtilis that carries in its genome a staphylococcal chloramphenicol acetyltransferase gene (from pC194) responds to growth at different concentrations of chloramphenicol by an alteration in the number of copies per genome of the sequences encoding the gene. Growth at 20 micrograms chloramphenicol ml-1 results in a 15-fold amplification of the sequences, whereas growth in the absence of chloramphenicol results in their loss. The mechanism of in situ amplification probably has much in common with that involved in 'R factor transitioning'. The hybridization procedures that have been used for accurately determining the number of copies of the amplified DNA sequences are potentially useful for plasmid copy number determination. The findings reported here also provide a potentially useful alternative to more conventional cloning strategies that are based on autonomous plasmids in B. subtilis. The particular advantages that can be envisaged include enhanced stability of the cloned sequences and control of the number of copies that are present.
New directions in single-molecule imaging and analysis (2007)

Optical imaging and analysis of single molecules continue to unfold as powerful ways to study the individual behavior of biological systems, unobscured by ensemble averaging. Current expansion of interest in this field is great, as evidenced by new meetings, journal special issues, and the large number of new investigators. Selected recent advances in biomolecular analysis are described, and two new research directions are summarized: superresolution imaging using single-molecule fluorescence and trapping of single molecules in solution by direct suppression of Brownian motion.
Characterization of Carotid Plaque Hemorrhage (2010)

CTA plaque ulceration, but not mean CTA plaque density, was useful for prediction of IPH as defined by the MR-IPH technique.
Silicon optical modulators at 1.3- mu m based on free-carrier absorption (1991)

Silicon optical waveguide modulators, appropriate for operation in the 1.3-1.55 mu m wavelength region, have been fabricated and their performance characterized at the wavelength of 1.3 mu m. The modulator structures consist of p-i-n diodes integrated with silicon waveguides; device operation is based on free-carrier absorption. Modulation depths of -6.2 dB and response times less than 50 ns have been measured. Experimental results are compared with the p-i-n diode theory. It is argued that the device is suitable for integration with silicon electronics and silicon optoelectronic devices. The response times measured for the current devices may be improved by reducing the transverse dimensions of the p-i-n structure.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A vector for systematic gene inactivation in Bacillus subtilis (1998)

To study the functions of the uncharacterized open reading frames identified in the Bacillus subtilis genome, several vectors were constructed to perform insertional mutagenesis in the chromosome. All the pMUTIN plasmids carry a lacZ reporter gene and an inducible Pspac promoter, which is tightly regulated and can be induced about 1000-fold. The integration of a pMUTIN vector into the target gene has three consequences: (1) the target gene is inactivated; (2) lacZ becomes transcriptionally fused to the gene, allowing its expression pattern to be monitored; (3) the Pspac promoter controls the transcription of downstream genes in an IPTG-dependent fashion. This last feature is important because B. subtilis genes are often organized in operons. The potential polar effects generated by the integration of the vectors can be alleviated by addition of IPTG. Also, conditional mutants of essential genes can be obtained by integrating pMUTIN vectors upstream of the target gene. The vectors are currently being used for systematic inactivation of genes without known function within the B. subtilis European consortium. pMUTIN characteristics and the inactivation of eight genes in the resA-serA region of the chromosome are presented.
Functional Characteristics of ES Cell–derived Cardiac Precursor Cells Identified by Tissue-specific Expression of the Green Fluorescent Protein (1998)

In contrast to terminally differentiated cardiomyocytes, relatively little is known about the characteristics of mammalian cardiac cells before the initiation of spontaneous contractions (precursor cells). Functional studies on these cells have so far been impossible because murine embryos of the corresponding stage are very small, and cardiac precursor cells cannot be identified because of the lack of cross striation and spontaneous contractions. In the present study, we have used the murine embryonic stem (ES, D3 cell line) cell system for the in vitro differentiation of cardiomyocytes. To identify the cardiac precursor cells, we have generated stably transfected ES cells with a vector containing the gene of the green fluorescent protein (GFP) under control of the cardiac alpha-actin promoter. First, fluorescent areas in ES cell-derived cell aggregates (embryoid bodies [EBs]) were detected 2 d before the initiation of contractions. Since Ca2+ homeostasis plays a key role in cardiac function, we investigated how Ca2+ channels and Ca2+ release sites were built up in these GFP-labeled cardiac precursor cells and early stage cardiomyocytes. Patch clamp and Ca2+ imaging experiments proved the functional expression of the L-type Ca2+ current (ICa) starting from day 7 of EB development. On day 7, using 10 mM Ca2+ as charge carrier, ICa was expressed at very low densities 4 pA/pF. The biophysical and pharmacological properties of ICa proved similar to terminally differentiated cardiomyocytes. In cardiac precursor cells, ICa was found to be already under control of cAMP-dependent phosphorylation since intracellular infusion of the catalytic subunit of protein kinase A resulted in a 1.7-fold stimulation. The adenylyl cyclase activator forskolin was without effect. IP3-sensitive intracellular Ca2+ stores and Ca2+-ATPases are present during all stages of differentiation in both GFP-positive and GFP-negative cells. Functional ryanodine-sensitive Ca2+ stores, detected by caffeine-induced Ca2+ release, appeared in most GFP-positive cells 1-2 d after ICa. Coexpression of both ICa and ryanodine-sensitive Ca2+ stores at day 10 of development coincided with the beginning of spontaneous contractions in most EBs. Thus, the functional expression of voltage-dependent L-type Ca2+ channel (VDCC) is a hallmark of early cardiomyogenesis, whereas IP3 receptors and sarcoplasmic Ca2+-ATPases are expressed before the initiation of cardiomyogenesis. Interestingly, the functional expression of ryanodine receptors/sensitive stores is delayed as compared with VDCC.