gebhart/patrepeval huggingface dataset:
Natural Killer Cells and Neuroblastoma: Tumor Recognition, Escape Mechanisms, and Possible Novel Immunotherapeutic Approaches (2014)

Neuroblastoma (NB) is the most common extra-cranial solid tumor of childhood and arises from developing sympathetic nervous system. Most primary tumors localize in the abdomen, the adrenal gland, or lumbar sympathetic ganglia. Amplification in tumor cells of MYCN, the major oncogenic driver, patients' age over 18 months, and the presence at diagnosis of a metastatic disease (stage IV, M) identify NB at high risk of treatment failure. Conventional therapies did not significantly improve the overall survival of these patients. Moreover, the limited landscape of somatic mutations detected in NB is hampering the development of novel pharmacological approaches. Major efforts aim to identify novel NB-associated surface molecules that activate immune responses and/or direct drugs to tumor cells and tumor-associated vessels. PVR (Poliovirus Receptor) and B7-H3 are promising targets, since they are expressed by most high-risk NB, are upregulated in tumor vasculature and are essential for tumor survival/invasiveness. PVR is a ligand of DNAM-1 activating receptor that triggers the cytolytic activity of natural killer (NK) cells against NB. In animal models, targeting of PVR with an attenuated oncolytic poliovirus induced tumor regression and elimination. Also B7-H3 was successfully targeted in preclinical studies and is now being tested in phase I/II clinical trials. B7-H3 down-regulates NK cytotoxicity, providing NB with a mechanism of escape from immune response. The immunosuppressive potential of NB can be enhanced by the release of soluble factors that impair NK cell function and/or recruitment. Among these, TGF-β1 modulates the cytotoxicity receptors and the chemokine receptor repertoire of NK cells. Here, we summarize the current knowledge on the main cell surface molecules and soluble mediators that modulate the function of NK cells in NB, considering the pros and cons that must be taken into account in the design of novel NK cell-based immunotherapeutic approaches.
The Hemophilias — From Royal Genes to Gene Therapy (2001)

Of the various types of hemophilia, the most common of these lifelong bleeding disorders are due to an inherited deficiency of factor VIII or factor IX (Table 1). The genes for these blood coagulation factors lie on the X chromosome, and when mutated, they cause the X-linked recessive traits hemophilia A and B. Since these disorders are X-linked, they usually occur in males. Usually, the affected boy has inherited the mutant gene (XH ) from his carrier mother (X H/X ), but about 30 percent of cases arise from a spontaneous mutation, and there is . . .
High-speed low-voltage single-drive push-pull silicon Mach-Zehnder modulators (2012)

We demonstrate a single-drive push-pull silicon Mach-Zehnder modulator (MZM) with a π-phase-shift voltage of 3.1 V and speed up to 30 Gb/s. The on-chip insertion loss is 9 dB due to the use of a 6 mm-long phase shifter. Higher switching speed up to 40-50 Gb/s is also demonstrated in devices with shorter phase shifters which require higher drive voltages but have lower insertion losses.
A low-noise CMOS interface circuit for closed-loop accelerometer (2009)

In this paper, design and characterization of a 18 V switched-capacitor CMOS interface circuit for the closed-loop operation of a capacitive accelerometer is presented. The pendulous silicon accelerometer operates in atmosphere pressure and is designed for non-peaking (low-Q) response with a sensitivity of 0.5 pF/g without vacuum packaging. Test results shows that a full scale acceleration of plusmn15 g and a signal bandwidth of 300 Hz is achieved. The complete module operates from a single 18 V supply and has a measured sensitivity of 420 mV/g with a noise of floor of 10 mug/radic(Hz) in closed-loop. The chip is fabricated in the 2 mum two-metal and two-poly n-well CMOS process with an area of 15.2 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> .
Epidemiology of Aflatoxin Formation by Aspergillus Flavus* (1987)

Beneficial microbes in the microbiome of plant roots improve plant health. Induced systemic resistance (ISR) emerged as an important mechanism by which selected plant growth–promoting bacteria and fungi in the rhizosphere prime the whole plant body for ...Read More
Conjugation and Genetic Exchange in Enterococci (2014)

The medical importance of the enterococci is closely related to the propensity of these organisms to participate in the horizontal transfer of determinants for antibiotic resistance and virulence. Conjugative plasmids in enterococci tend to fall into two main groups. Members of one group encode recognition of recipient-produced peptide pheromones that initiate the mating process; the others do not make use of such signals. The pheromone-responding plasmids usually transfer efficiently in broth (liquid) matings, whereas the others transfer relatively poorly under these conditions. An exception is pMGl, a resistance plasmid in Enterococcus faecium that transfers well in broth despite the apparent absence of a pheromone system. Those plasmids that make use of sex pheromones (e.g., pADl and pCFlO) thus far appear to exhibit a narrow host range—primarily Enterococcus faecalis and closely related species-although information on this point is very limited. A partial list of pheromone-responding plasmids is presented in this chapter. The formation of mating aggregates relates to the induction of a protein aggregation substance (AS), which appears extensively over the donor surface and binds to enterococcal binding substance (EBS) on the recipient surface. Conjugative transposons are particularly common in enterococci and streptococci and play an important role in the dissemination of antibiotic resistance in these organisms. It is likely that the enterococci play a significant role as a hardy facultative reservoir of genetic information available to a variety of other genera.
Modular Nucleic Acid Surrogates. Solid Phase Synthesis of α-Helical Peptide Nucleic Acids (αPNAs) (1999)

[formula: see text] The synthesis and characterization of prototype alpha-helical peptide nucleic acid (alpha PNA) modules 1-3 as well as disulfide dimers 4 and 5 are reported. These molecules combine an alpha-helical peptidyl scaffold with well-defined nucleobase molecular recognition patterns and could serve as a basis for novel antisense and/or antigene agents. Structure assignments for these alpha PNAs were supported by MALDI-TOF mass spectrometry, and the alpha-helical nature of 4 in water was confirmed by circular dichroism (CD) spectroscopy.
The Eukaryotic Promoter Database, EPD: new entry types and links to gene expression data (2002)

The Eukaryotic Promoter Database (EPD) is an annotated, non-redundant collection of eukaryotic Pol II promoters, for which the transcription start site has been determined experimentally. Access to promoter sequences is provided by pointers to positions in nucleotide sequence entries. The annotation part of an entry includes a description of the initiation site mapping data, exhaustive cross-references to the EMBL nucleotide sequence database, SWISS-PROT, TRANSFAC and other databases, as well as bibliographic references. EPD is structured in a way that facilitates dynamic extraction of biologically meaningful promoter subsets for comparative sequence analysis. World Wide Web-based interfaces have been developed which enable the user to view EPD entries in different formats, to select and extract promoter sequences according to a variety of criteria, and to navigate to related databases exploiting different cross-references. The EPD web site also features yearly updated base frequency matrices for major eukaryotic promoter elements. EPD can be accessed at http://www.epd.isb-sib.ch.
Macrophages Switch to an Osteo‐Modulatory Profile Upon RANKL Induction in a Medaka ( Oryzias latipes ) Osteoporosis Model (2020)

In mammals, osteoclasts differentiate from macrophages in the monocyte lineage. Although many factors driving osteoclast formation are known, the detailed processes underlying precursor recruitment, differentiation, and interaction of macrophages with other cell types involved in bone remodeling are poorly understood. Using live imaging in a transgenic medaka osteoporosis model, where ectopic osteoclasts are induced by RANKL expression, we show that a subset of macrophages is recruited to bone matrix to physically interact with bone-forming osteoblast progenitors. These macrophages subsequently differentiate into <i>cathepsin K-</i> (<i>ctsk-</i>) positive osteoclasts. One day later, other macrophages are recruited to clear dying osteoclasts from resorbed bone by phagocytosis. To better understand the molecular changes underlying these dynamic processes, we performed transcriptome profiling of activated macrophages upon RANKL induction. This revealed an upregulation of several bone-related transcripts. Besides osteoclast markers, we unexpectedly also found expression of osteoblast-promoting signals in activated macrophages, suggesting a possible non-cell autonomous role in osteogenesis. Finally, we show that macrophage differentiation into osteoclasts is dependent on inflammatory signals. Medaka deficient for TNFα or treated with the TNFα-inhibitor pentoxifylline exhibited impaired macrophage recruitment and osteoclast differentiation. These results show the involvement of inflammatory signals and the dynamics of a distinct subset of macrophages during osteoclast formation. © 2020 The Authors. <i>JBMR Plus</i> published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
No common denominator for breast cancer lymph node metastasis (2005)

The axillary lymph node status is the most powerful prognostic factor for breast cancer patients to date. The molecular mechanisms that control lymph node metastasis, however, remain poorly understood. To define patterns of genes or gene regulatory pathways that drive breast cancer lymph node metastasis, we compared the gene expression profiles of 15 primary breast carcinomas and their matching lymph node metastases using microarrays. In general, primary breast carcinomas and lymph node metastases do not differ at the transcriptional level by a common subset of genes. No classifier or single gene discriminating the group of primary tumours from those of the lymph node metastases could be identified. Also, in a series of 295 breast tumours, no classifier predicting lymph node metastasis could be developed. However, subtle differences in the expression of genes involved in extracellular-matrix organisation and growth factor signalling are detected in individual pairs of matching primary and metastatic tumours. Surprisingly, however, different sets of these genes are either up- or downregulated in lymph node metastases. Our data suggest that breast carcinomas do not use a shared gene set to accomplish lymph node metastasis.
IRAK1 and IRAK4 Promote Phosphorylation, Ubiquitination, and Degradation of MyD88 Adaptor-like (Mal) (2010)

Signal transduction by Toll-like receptor 2 (TLR2) and TLR4 requires the adaptors MyD88 and Mal (MyD88 adaptor-like) and serine/threonine kinases, interleukin-1 receptor-associated kinases IRAK1 and IRAK4. We have found that both IRAK1 and IRAK4 can directly phosphorylate Mal. In addition, co-expression of Mal with either IRAK resulted in depletion of Mal from cell lysates. This is likely to be due to Mal phosphorylation by the IRAKs because kinase-inactive forms of either IRAK had no effect. Furthermore, lipopolysaccharide stimulation resulted in ubiquitination and degradation of Mal, which was inhibited using an IRAK1/4 inhibitor or by knocking down expression of IRAK1 and IRAK4. MyD88 is not a substrate for either IRAK and did not undergo degradation. We therefore conclude that Mal is a substrate for IRAK1 and IRAK4 with phosphorylation promoting ubiquitination and degradation of Mal. This process may serve to negatively regulate signaling by TLR2 and TLR4.
Nitric Oxide–Induced Apoptosis in Human Leukemic Lines Requires Mitochondrial Lipid Degradation and Cytochrome C Release (1999)

We have previously shown that nitric oxide (NO) stimulates apoptosis in different human neoplastic lymphoid cell lines through activation of caspases not only via CD95/CD95L interaction, but also independently of such death receptors. Here we investigated mitochondria-dependent mechanisms of NO-induced apoptosis in Jurkat leukemic cells. NO donor glycerol trinitrate (at the concentration, which induces apoptotic cell death) caused (1) a significant decrease in the concentration of cardiolipin, a major mitochondrial lipid; (2) a downregulation in respiratory chain complex activities; (3) a release of the mitochondrial protein cytochrome c into the cytosol; and (4) an activation of caspase-9 and caspase-3. These changes were accompanied by an increase in the number of cells with low mitochondrial transmembrane potential and with a high level of reactive oxygen species production. Higher resistance of the CD95-resistant Jurkat subclone (APO-R) cells to NO-mediated apoptosis correlated with the absence of cytochrome c release and with less alterations in other mitochondrial parameters. An inhibitor of lipid peroxidation, trolox, significantly suppressed NO-mediated apoptosis in APO-S Jurkat cells, whereas bongkrekic acid (BA), which blocks mitochondrial permeability transition, provided only a moderate antiapoptotic effect. Transfection of Jurkat cells with bcl-2 led to a complete block of apoptosis due to the prevention of changes in mitochondrial functions. We suggest that the mitochondrial damage (in particular, cardiolipin degradation and cytochrome c release) induced by NO in human leukemia cells plays a crucial role in the subsequent activation of caspase and apoptosis.
The Role of Passive Transbilayer Drug Movement in Multidrug Resistance and Its Modulation (1996)

The successful lowering of the intracellular concentration of multidrug resistance (MDR)-type drugs by P-glycoprotein (Pgp) relies on its ability to overcome the passive influx rate of each MDR-type drug. Thus, the aim of the present work was to study the effect of passive transbilayer drug movement on the multidrug resistance and its modulation. Fluorescence quenching studies indicated that whereas the Pgp substrate rhodamine 123 traverses an artificial lipid membrane with a lifetime of 3 min, the transbilayer movement rate of the MDR modulators, quinidine and quinine, was too fast to be detected with present methods. Transbilayer movement rates of drugs and modulators were estimated from their equilibration rate throughout artificial multilamellar vesicles. The equilibration rate of five selected modulators was faster than the equilibration rate of five representative MDR-type drugs tested, which was comparable with the rate of rhodamine 123 equilibration. Moreover, the carrier-type peptide ionophore, valinomycin, which is freely mobile in the membrane, inhibited Pgp-mediated efflux of rhodamine 123 from MDR cells. In contrast, the channel-forming ionophore gramicidin D, a Pgp substrate that flip-flops slowly across the membrane, did not modulate cellular Pgp activity. Pgp, with a turnover number of about 900 min-1 can keep pace with the influx of an MDR-drug like rhodamine 123 exhibiting a transbilayer movement with a lifetime of minutes. On the other hand, Pgp would fail to protect MDR cells against cytotoxic drugs that are freely mobile through biological membranes and that re-enter cells faster than their Pgp-mediated active efflux rate. The relatively fast transbilayer movement exhibited by MDR modulators suggest that in contrast to MDR-type drugs, MDR modulators traverse the plasma membrane faster than the maximal expulsion rate of Pgp.
Two-stage chemical oncogenesis in cultures of C3H/10T1/2 cells. (1976)

The initiation and promotion stages of chemical oncogenesis have been demonstrated in cultured C3H/10T1/2 mouse embryo cells. Treatment of the cells with a subeffective concentration of 3-methylcholanthrene, benzo(a)pyrene, or 7,12-dimethylbenz(a)anthracene, followed 4 days later by a nontransforming amount of tetradecanoylphorbol acetate (TPA), phorbol didecanoate, or 4-alpha-phorbol didecanoate, produced transformation. Phorbol was ineffective. TPA did not select for transformed cells. When TPA treatment preceded 3-methylcholanthrene, no enhancement of transformation was observed. When TPA was added immediately after hydrocarbon treatment, there was a significant inhibition of transformation. TPA did not exert promoting activity when the hydrocarbons were in high enough concentrations to produce appreciable transformation. The promoting action of TPA cannot be attributed only to a stimulation of cell division.
[The evaluation in hamadryas baboons of the possibility for the specific prevention of Ebola fever]. (1994)

The protective role of virus-neutralizing antibody was demonstrated in Ebola virus-infected animals (Papio hamadryas) used in experiments on the development of passive humoral immunity by using specific immunoglobulin. Two immunizations of the monkeys with purified concentrated Ebola virus antigen with complete Freund adjuvant was shown to confirm intensive immunity to subsequent challenge protecting 80% of the immunized animals. It is concluded that effective preparations may be developed for specific prophylaxis of Ebola fever.
Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans (2009)

Studies in animals have documented that, compared with glucose, dietary fructose induces dyslipidemia and insulin resistance. To assess the relative effects of these dietary sugars during sustained consumption in humans, overweight and obese subjects consumed glucose- or fructose-sweetened beverages providing 25% of energy requirements for 10 weeks. Although both groups exhibited similar weight gain during the intervention, visceral adipose volume was significantly increased only in subjects consuming fructose. Fasting plasma triglyceride concentrations increased by approximately 10% during 10 weeks of glucose consumption but not after fructose consumption. In contrast, hepatic de novo lipogenesis (DNL) and the 23-hour postprandial triglyceride AUC were increased specifically during fructose consumption. Similarly, markers of altered lipid metabolism and lipoprotein remodeling, including fasting apoB, LDL, small dense LDL, oxidized LDL, and postprandial concentrations of remnant-like particle-triglyceride and -cholesterol significantly increased during fructose but not glucose consumption. In addition, fasting plasma glucose and insulin levels increased and insulin sensitivity decreased in subjects consuming fructose but not in those consuming glucose. These data suggest that dietary fructose specifically increases DNL, promotes dyslipidemia, decreases insulin sensitivity, and increases visceral adiposity in overweight/obese adults.
Vitamin E analogues as anti-cancer agents: The role of modulation of apoptosis signalling pathways (2006)

Summary Recently, considerable decrease in a number of previously fatal pathologies has been achieved, largely due to the advancement in molecular medicine and due to modern approaches to treatment. In spite of this success, neoplastic disease remains a serious problem for several reasons. These include an exceedingly high variability of cancer cells even within the same type of tumor. Cancer cells, albeit of clonal origin, mutate so that they escape established treatments, resulting in the fatal outcome of current therapies. Moreover, there are types of cancer, such as mesotheliomas, that cannot be treated at present. A novel group of clinically interesting anti-cancer drugs has been a recent focus in the literature that hold substantial promise as selective anti-cancer agents. These compounds, epitomized by α-tocopheryl succinate, comprise redox-silent analogs of vitamin E that have been shown to suppress several types of cancer in animal models, including breast, colon and lung cancer as well as mesotheliomas and melanomas, while being non-toxic to normal cells and tissues. It is now proven that the strong anti-cancer effect of vitamin E analogs stems from their propensity to induce selective apoptosis in malignant cells. The results point to the novel group of vitamin E analogs as promising agents applicable to different types of tumors.
Mucosal immunization with recombinant adenoviruses: induction of immunity and protection of cotton rats against respiratory bovine herpesvirus type 1 infection. (1997)

To facilitate the evaluation of vaccines against bovine herpesvirus type 1 (BHV-1), a cotton rat model of intranasal (i.n.) BHV-1 infection was established. Cotton rat lung cells were similar to bovine cells in their ability to support BHV-1 replication in vitro. Furthermore, i.n. inoculation of cotton rats with BHV-1 resulted in pulmonary lesions comparable to BHV-1 infection in cattle. Using this model, the potential of i.n. and gastrointestinal (g.i.) immunization was examined with recombinant human adenoviruses expressing glycoprotein D (gD) of BHV-1 to induce protective immunity against BHV-1. The replication-competent virus (gD-dE3) was more efficient than the replication-defective virus (gD-dE1E3) in inducing gD-specific antibody in the serum and in the respiratory tract. Furthermore, i.n. immunization with gD-dE3 stimulated antigen-specific antibody-secreting cells in the lung 12 weeks following immunization. Protection against BHV-1 challenge correlated with gD-specific antibody levels such that i.n. immunization with gD-dE3 conferred complete protection, while g.i. immunization conferred only partial protection of the lungs of most animals against BHV-1 challenge. In comparison, immunization with gD-dE1E3 by either route resulted in only a partial reduction of BHV-1 titre in the respiratory tract. The results obtained demonstrate that mucosal immunization with replication-competent recombinant adenovirus expressing gD of BHV-1 can induce immunity and protection against BHV-1 challenge.
An improved frequency offset estimator for OFDM applications (1999)

An efficient algorithm has been proposed by Schmidl and Cox (see IEEE Trans. Commun., vol.45, p.1613-21, 1997) for carrier frequency estimation in orthogonal frequency-division multiplexing systems. The scheme is based on the transmission of a training symbol composed of two identical halves in the time domain. We extend this algorithm by considering a training symbol composed of L>2 identical parts. This makes it possible to achieve a better accuracy at the cost of some increase in computational load. The estimation range can be made as large as desired without the need of a second training symbol, as required by the Schmidl and Cox method.
Variable major proteins of Borrelia hermsii. Epitope mapping and partial sequence analysis of CNBr peptides. (1985)

The variable major proteins (VMP) of serotypes 7 and 21 of the relapsing fever agent Borrelia hermsii were isolated by detergent extraction and high performance liquid chromatography. Cyanogen bromide (CNBr) digestion of the isolated VMP yielded two peptides of apparent molecular weights 20,000 (20 K) and 16 K from VMP7, and three peptides of 14.5, 14, and 7 K mol wt from VMP21. Serotype-specific monoclonal antibodies bound in Western blots to one of each of the two or three CNBr fragments from the homologous VMP. A single monoclonal antibody bound to the whole cells, the isolated VMP, and a CNBr fragment of both serotype 7 and serotype 21. (This crossreactive antibody did not, however, bind to any of four other serotypes examined.) Regional conservation of structure between VMP7 and VMP21 was also shown by amino acid sequence analysis of the N-termini of the five CNBr fragments. One pair of aligned fragments from VMP7 and VMP21 had 80% amino acid homology in sequence; a second pair had 40% homology. The partial amino acid homologies between two VMP suggest that these proteins are products of members of a polygene family.