gebhart/patrepeval huggingface dataset:
A point mutation of human interferon γ abolishes receptor recognition (1992)

We identified a single amino acid mutation that abolished the bioactivity of human IFN gamma. The mutation was identified by screening a mutagenized IFN gamma expression library for molecules with altered biological activity. The mutant protein was expressed at high levels in Escherichia coli, and remained soluble upon purification. However, the protein was completely inactive in all IFN gamma assays investigated, exhibiting less than 0.0006% of the specific activity of native IFN gamma antiviral activity. Sequencing the plasmid DNA encoding this mutant protein showed that the histidine at position 111 of native human IFN gamma is changed to aspartic acid (IFN gamma/H111D). Other mutations at this site showed that only hydrophobic amino acids at position 111 maintain significant, though low, biological activity. Structural characterization of the IFN gamma/H111D protein by NMR as well as CD spectroscopy demonstrated that the protein has limited conformational differences from native IFN gamma. Models of the X-ray crystal structure of human IFN gamma [Ealick, P.E., W.J. Cook, S. Vijay-Kumar, M. Carson, T.L. Nagabhushan, P.P. Trotta and C.E. Bugg (1991) Science, 252, 698-702] suggest that this histidine residue is located at a severe 55 degrees bend in the C-terminal F helix. We conclude that H111 lies within or affects the receptor binding domain of human IFN gamma.
Genipin‐Modified Silk‐Fibroin Nanometric Nets (2008)

Nanometric silk-fibroin nets were fabricated by electrospinning from regenerated Bombyx mori silk-fibroin (SF)/formic acid solutions with the addition of genipin (GE), 2, 15 and 24 h after the solution preparation. After spinning, the pure fibroin nanofibers were water soluble and needed a further stabilization process, whereas the reaction of fibroin with genipin resulted in water-insoluble fibroin nets due to conformational changes induced in the fibroin by the genipin. SFGE nanofibers presented diameters ranging from 140 to 590 nm and were generally thinner than pure SF nanofibers. The secondary structure of SF into SFGE nanofibers showed the presence of a beta-sheet conformation together with beta-turn intermediates (turns and bends). The approach described in this paper provides an alternative method of designing SF nanofibers that are already water insoluble, without any stability post-treatment needed.
Tight association of hepatocellular carcinoma with HBV infection in North China. (2005)

HBV infection is virtually ubiquitous in HCC patients in North China. The tight association of HBV with HCC strongly suggests the dominant role of HBV infection in causing hepatocellular carcinoma. About 11.8% of HCC patients being HCV-related are co-infected with HBV.
Monocular SLAM as a Graph of Coalesced Observations (2007)

We present a monocular SLAM system that avoids inconsistency by coalescing observations into independent local coordinate frames, building a graph of the local frames, and optimizing the resulting graph. We choose coordinates that minimize the nonlinearity of the updates in the nodes, and suggest a heuristic measure of such nonlinearity, using it to guide our traversal of the graph. The system operates in real-time on sequences with several hundreds of landmarks while performing global graph optimization, yielding accurate and nearly consistent estimation relative to offline bundle adjustment, and considerably better consistency than EKF SLAM and FastSLAM.
An FDMA system concept for 30/20 GHz high capacity domestic satellite service (1982)

The paper summarizes a feasibility study of a multibeam FDMA satellite system operating in the 30/20 GHz band. The system must accommodate a very high volume of traffic within the restrictions of a 5 kW solar cell array and a 2.5 GHz bandwidth. Multibeam satellite operation reduces the DC power demand and allows reuse of the available bandwidth. Interferences among the beams are brought to acceptable levels by appropriate frequency assignments. A transponder design is presented; it is greatly simplified by the application of a regional concept. System analysis shows that MSK modulation is appropriate for a high-capacity system because it conserves the frequency spectrum. Rain attenuation, a serious problem in this frequency band, is combatted with sufficient power margins and with coding. Link budgets, cost analysis, and weight and power calculations are also discussed. A satellite-routed FDMA system compares favorably in performance and cost with a satellite-switched TDMA system.
Peptide binding by protein disulfide isomerase, a resident protein of the endoplasmic reticulum lumen. (1991)

Previously we had demonstrated by photoaffinity labeling that a 57-kDa protein of the endoplasmic reticulum can bind and become covalently linked to glycosylatable photoreactive peptides containing the sequence-Asn-Xaa-Ser/Thr-. Subsequently, it was found that this protein, called glycosylation site-binding protein, was a multifunctional protein, i.e. it was identical to protein disulfide isomerase (PDI), the beta-subunit of prolyl hydroxylase and thyroid hormone-binding protein. In this study, the peptide specificity for binding to this 57-kDa protein, hereafter called PDI, has been investigated in more detail using photoaffinity probes. The results reveal that although N-glycosylation by oligosaccharyl transferase in the endoplasmic reticulum has an absolute requirement for an hydroxyamino acid in the third amino acid residue of the glycosylation site sequence, no such specificity is observed in the binding of such peptides to PDI. In addition to the lack of specificity for an hydroxyamino acid in the third residue position, no specificity was observed for the asparagine residue in the first position. Thus, binding is not restricted to peptides containing N-glycosylation sites. We have investigated the discrepancy between this apparent lack of sequence specificity and earlier results indicating that binding of peptides to PDI was specific for N-glycosylation site sequences. We now demonstrate that PDI in the lumen of microsomes is more efficiently labeled by peptides containing photoreactive-Asn-Xaa-Ser/Thr- sequences than by nonacceptor site sequences because the former become glycosylated. This increased labeling does not occur because the glycosylated form of the probes are preferentially recognized by PDI. Rather, it appears that increased polarity of the affinity probe after attachment of the oligosaccharide chain prevents its exit from the sealed microsomes, in effect concentrating it within the lumen of the microsome. These results, coupled with other studies on the multifunctional nature of PDI, suggest that the observed peptide binding may be a manifestation of the ability of PDI to recognize the backbone of polypeptides in the lumen of the endoplasmic reticulum.
Performance of an Efficient Parallel Data Transmission System (1967)

A parallel quadrature AM data transmission system may be implemented with a number of overlapping channels, each carrying a signaling rate <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">b</tex> , spaced <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">b/2</tex> apart in frequency. When a large number of channels are used, the system allows transmission speeds very close to the Nyquist rate, with little sensitivity to delay and amplitude distortion of the transmission medium. The receiver requires precise phasing of the demodulating carriers and sampling times in order to keep crosstalk between channels small. In the presence of delay and amplitude distortion, better results are obtained when half cosine roll-offs are used for shaping each channel than for full cosine roll-off. This transmission scheme appears to be a promising technique for achieving good performance at high information rates over bandlimited dispersive transmission media.
Clinical Applications for microRNAs in Cancer (2012)

The discovery that noncoding components of the genome, including microRNA (miRNA or miR), can contribute to the pathogenesis of cancer has led investigators to contemplate using these molecules to guide clinical decision making. Currently, miRNA signatures are being applied in human clinical trials and miRNA-directed therapy is under way, with miR-122 targeting in hepatitis C (HCV) being the most developed therapy thus far. miRNA-based targeting in cancer is not far behind, with several private companies developing therapeutics. We are recognizing the potential for miRNA biology to clarify both the molecular pathogenesis of cancer and the inherent complexities in translating its biology to clinics. An increased understanding of fundamental miRNA biology, improved bioinformatics, and directed in vivo targeting while minimizing off-target effects and toxicity will be required for successful translational application. Here, we provide an overview of miRNAs, with a focus on aspects of translating bench-based discoveries to the clinic.
Interleukin-7, a Non-Redundant Potent Cytokine whose Over-Expression Massively Perturbs B-Lymphopoiesis (1998)

Interleukin-7, originally described as a factor controlling the survival of B-cell progenitors, has been shown by gene knock-out technology to be a non-redundant cytokine. Of all single cytokine knock-out mice, those in which the IL-7 gene has been ablated show a profound defect in lymphocyte development. Likewise, mice in which signals emanating from the corresponding receptor, whether it be by ablation of the unique alpha or common gamma chain of the receptor, or by interference with downstream signalling elements generated by this receptor complex, also show profound defects in lymphocyte differentiation. Transgenic mice over-expressing the IL-7 gene also show profound changes in lymphocyte development which, in some instances can result in the development of lymphoid tumours. Here, we review some of these aspects of IL-7 biology with particular reference to an IL-7 over-expressing transgenic mouse line in which the IL-7 transgene is controlled by the mouse MHC class II promoter.
Presence of human papillomavirus DNA and abnormal p53 protein accumulation in lung carcinoma. (1996)

p53 plays an important part in the development of lung carcinomas and, in some cases, HPV may contribute to it by binding and inactivating the p53 protein.
Niacinamide - Mechanisms of Action and Its Topical Use in Dermatology (2014)

Niacinamide, an amide of vitamin B3 (niacin), is a hydrophilic endogenous substance. Its effects after epicutaneous application have long been described in the literature. Given a sufficient bioavailability, niacinamide has antipruritic, antimicrobial, vasoactive, photo-protective, sebostatic and lightening effects depending on its concentration. Within a complex metabolic system niacinamide controls the NFκB-mediated transcription of signalling molecules by inhibiting the nuclear poly (ADP-ribose) polymerase-1 (PARP-1). Niacinamide is a well-tolerated and safe substance often used in cosmetics. Clinical data for its therapeutic use in various dermatoses can increasingly be found in the literature. Although the existing data are not sufficient for a scientifically founded evaluation, it can be stated that the use of niacinamide in galenic preparations for epicutaneous application offers most interesting prospects.
SNPinProbe_1.0: A database for filtering out probes in the Affymetrix GeneChip® Human Exon 1.0 ST array potentially affected by SNPs (2008)

http://cid-fb2a64e541add2be.skydrive.live.com/browse.aspx/Affy%7C_HuEx%7C_1.0ST?uc=2.
RANKL/RANK/OPG: Key Therapeutic Target in Bone Oncology (2008)

Cancer is one of the major leading causes of death all over the world. Primary and secondary bone tumors can significantly deteriorate the quality of life (QOL) and the activity of daily living (ADL) of the patients. These unwelcome diseases become a social and economic burden seriously. Thus, more effective therapies for both primary and secondary bone tumors are actually required. Bone homeostasis depends on the strictly balanced activities between bone formation by osteoblasts and bone resorption by osteoclasts. Imbalance of bone formation and resorption results in various bone diseases. Both primary and secondary bone tumors develop in the unique environment bone, it is therefore necessary to understand bone cell biology in tumoral bone environment. Recent findings strongly revealed the significant involvement of the receptor activator of nuclear factor kappaB ligand (RANKL)/RANK/osteoprotegerin (OPG) triad, the key regulators of bone remodeling in bone oncology. Indeed, RANKL/RANK blocking successfully prevented the development of bone metastases. Furthermore, some cancer cells express RANK which is involved in tumor cell migration. Thus, the regulation of this triad will be a rational, encouraged therapeutic hot spot in bone oncology. In this review, we summarize the accumulating knowledge of the RANKL/RANK/OPG triad and discuss about its therapeutic capability in primary and secondary bone tumors.
Intestinal colonization resistance (2012)

Dense, complex microbial communities, collectively termed the microbiota, occupy a diverse array of niches along the length of the mammalian intestinal tract. During health and in the absence of antibiotic exposure the microbiota can effectively inhibit colonization and overgrowth by invading microbes such as pathogens. This phenomenon is called 'colonization resistance' and is associated with a stable and diverse microbiota in tandem with a controlled lack of inflammation, and involves specific interactions between the mucosal immune system and the microbiota. Here we overview the microbial ecology of the healthy mammalian intestinal tract and highlight the microbe-microbe and microbe-host interactions that promote colonization resistance. Emerging themes highlight immunological (T helper type 17/regulatory T-cell balance), microbiota (diverse and abundant) and metabolic (short-chain fatty acid) signatures of intestinal health and colonization resistance. Intestinal pathogens use specific virulence factors or exploit antibiotic use to subvert colonization resistance for their own benefit by triggering inflammation to disrupt the harmony of the intestinal ecosystem. A holistic view that incorporates immunological and microbiological facets of the intestinal ecosystem should facilitate the development of immunomodulatory and microbe-modulatory therapies that promote intestinal homeostasis and colonization resistance.
Induction of cellular p53 activity by DNA-damaging agents and growth arrest. (1993)

The tumor suppressor p53 can function as a sequence-specific transcription factor and is required for activation by ionizing radiation (IR) of one or more downstream effector genes, such as the human GADD45 gene. One important consequence of IR that is probably mediated by these downstream effector genes is activation of the p53-mediated G1 cell cycle checkpoint. While the induction of reporter constructs containing p53-binding sites has already been demonstrated with p53 expression vectors, we have now demonstrated the direct activation of such a construct after treatment of the human RKO line, which has a normal p53 phenotype, with various types of DNA-damaging agents and also after growth arrest produced by medium depletion (starvation). IR, UV radiation, and methylmethane sulfonate were found to induce p53 activity when a stably integrated reporter construct containing functional p53-binding sites was used and also in mobility shift assays with a p53-binding site from the GADD45 gene, and IR-inducible gene previously associated with growth arrest. The same cell treatments that induced this p53 activity also caused an increase in cellular p53 protein levels. The response in cells lacking normal p53 or in RKO cells expressing a dominant negative mutant p53 was markedly reduced. Interestingly, the spectrum of effective inducing agents for the above-described experiments was similar to that which induces GADD45 either in cells with a normal p53 status or, with the exception of IR, in cells lacking normal p53. These results indicate a role for p53 in the IR pathway, which is completely p53 dependent, and in other genotoxic stress responses, in which p53 has a cooperative effect but is not required.
Development of intestinal organoids as tissue surrogates: Cell composition and the Epigenetic control of differentiation (2013)

Intestinal organoids are multicellular crypt-like structures that can be derived from adult intestinal stem cells (ISCs), embryonic stem cells (ESCs) or induced pluripotent stem cells (IPSCs). Here we show that intestinal organoids generated from mouse ESCs were enriched in ISCs and early progenitors. Treatment of these organoids with a γ-secretase inhibitor increased Math1 and decreased Hes1 expression, indicating Notch signaling regulates ISC differentiation in these organoids. Lgr5 and Tert positive ISCs constituted approximately 10% and 20% of the organoids. As found in native tissue, Lgr5 and Tert expressing cells resolved into two discreet populations, which were stable over time. Intestinal organoids derived from cancer-prone Apc(Min/+) mice showed similar numbers of ISCs, but had reduced Math1 expression, indicating a suppressed secretory cell differentiation potential (as found in intestinal tissue). Apc(Min/+) organoids were used to screen epigenetically active compounds for those that increased Math1 expression and organoid differentiation (including HDAC inhibitors, Sirtuin (SIRT) modulators and methyltransferase inhibitors). Broad-spectrum HDAC inhibitors increased both Math1 and Muc2 expression, indicating an ability to promote the suppressed secretory cell differentiation pathway. Other epigenetic compounds had a diverse impact on cell differentiation, with a strong negative correlation between those that activated the secretory marker Muc2 and those that activated the absorptive cell marker Fabp2. These data show that ESC-derived intestinal organoids can be derived in large numbers, contain distinct ISC types and can be used to screen for agents that promote cell differentiation through different lineage pathways.
Empirical risk minimization for support vector classifiers (2003)

In this paper, we propose a general technique for solving support vector classifiers (SVCs) for an arbitrary loss function, relying on the application of an iterative reweighted least squares (IRWLS) procedure. We further show that three properties of the SVC solution can be written as conditions over the loss function. This technique allows the implementation of the empirical risk minimization (ERM) inductive principle on large margin classifiers obtaining, at the same time, very compact (in terms of number of support vectors) solutions. The improvements obtained by changing the SVC loss function are illustrated with synthetic and real data examples.
Gene Expression Profiling in Uveal Melanoma Reveals Two Molecular Classes and Predicts Metastatic Death (2004)

Melanomas are notoriously difficult to classify because of a lack of discrete clinical and pathological stages. Here, we show that primary uveal melanomas surprisingly cluster into two distinct molecular classes based on gene expression profile. Genes that discriminate class 1 (low-grade) from class 2 (high-grade) include highly significant clusters of down-regulated genes on chromosome 3 and up-regulated genes on chromosome 8q, which is consistent with previous cytogenetic studies. A three-gene signature allows biopsy-size tumor samples to be assigned accurately to tumor classes using either array or PCR platforms. Most importantly, this molecular classification strongly predicts metastatic death and outperforms other clinical and pathological prognostic indicators. These studies offer new insights into melanoma pathogenesis, and they provide a practical foundation for effective clinical predictive testing.
A pH Electrode Based on Melt-Oxidized Iridium Oxide (2001)

Fabrication and characterization of a novel potentiometric pH electrode based on melt-oxidized iridium oxide film is presented. The oxide film produced in a lithium carbonate melt has the composition of and shows high chemical stability. The electrode based on this oxide film exhibits very promising pH sensing performance, with an ideal Nernstian response in the tested pH range of 1 to 13. The potential response is fast, with a 90% response time obtained in less than 1 s for all pH changes. The open-circuit potential of the electrode is almost drift-free, with an average variation over time in a pH 6.6 solution as small as 0.1 mV/day. Furthermore, the potential/pH slopes and the apparent standard electrode potentials show excellent agreement among electrodes from the same batch. A comparison is made of the present electrode and those reported in the literature with respect to fabrication method and pH sensing characteristics. © 2001 The Electrochemical Society. All rights reserved.
Self-replicating alphavirus RNA vaccines (2014)

Recombinant nucleic acids are considered as promising next-generation vaccines. These vaccines express the native antigen upon delivery into tissue, thus mimicking live attenuated vaccines without having the risk of reversion to pathogenicity. They also stimulate the innate immune system, thus potentiating responses. Nucleic acid vaccines are easy to produce at reasonable cost and are stable. During the past years, focus has been on the use of plasmid DNA for vaccination. Now mRNA and replicon vaccines have come into focus as promising technology platforms for vaccine development. This review discusses self-replicating RNA vaccines developed from alphavirus expression vectors. These replicon vaccines can be delivered as RNA, DNA or as recombinant virus particles. All three platforms have been pre-clinically evaluated as vaccines against a number of infectious diseases and cancer. Results have been very encouraging and propelled the first human clinical trials, the results of which have been promising.
Immunostimulatory Oligodeoxynucleotide Containing TTTCGTTT Motif from Lactobacillus rhamnosus GG DNA Potentially Suppresses OVA‐specific IgE Production in Mice (2008)

In a previous study of the immunoregulatory properties of commensal bacterial DNA, we identified the strong immunostimulatory oligodeoxynucleotide (ISS-ODN) ID35 in the genomic DNA of Lactobacillus rhamnosus GG (LGG). The observed effects of ID35 are because of the unique TTTCGTTT motif located at the 5' end of the ODN, which is different from the previously identified ISS motifs in humans and mice. In the present study, we used an ovalbumin (OVA)-sensitized mouse model to show that ID35 is a potent suppressor of antigen-specific immunoglobulin E (IgE) production in vivo. This effect was toll-like receptor 9-dependent, as GpC negID35 failed to suppress antigen-specific IgE production. ID35 activated the specific subset of CD11c+CD8a+ dendritic cells, which are associated with T-helper 1 (Th1)-type systemic responses, and effectively induced interferon-gamma (IFN-gamma) production by CD4+ T cells in OVA-challenged mice. These immunoregulatory effects of ID35 were comparable with those induced by the murine prototype ODN 1826. Thus, ID35 is the first ISS-ODN with such a strong immunostimulatory and IgE suppressor activity to be found in immunobiotic bacterial DNA.