gebhart/patrepeval huggingface dataset:
A comparative debate on the various anti-vascular endothelial growth factor drugs: Pegaptanib sodium (Macugen), ranibizumab (Lucentis) and bevacizumab (Avastin) (2007)

Wet age-related macular degeneration and diabetic retinopathy are pathological consequences of vascular endothelial growth factor (VEGF) release as a reaction to deficiency of oxygen and nutrients in the macular cells. Conventional treatment modalities have been constrained by limited success. Convincing evidence exists that targeting VEGF signaling is a significant approach for the therapy of these ocular angiogenesis-dependent disorders. We have come a long way since the approval of the first angiogenesis inhibitors in medicine. The clinical use of these drugs has provided enormous tempo to clinical and pharmacological research. It has also significantly altered patient outcome and expectations. In the following brief, we will discuss the development and emergence of these drugs as well as the anticipated future course based on evidence.
Quantitative Analysis of Proteome Coverage and Recovery Rates for Upstream Fractionation Methods in Proteomics (2010)

The proteome of any cell or even any subcellular fraction remains too complex for complete analysis by one dimension of liquid chromatography-tandem mass spectrometry (LC-MS/MS). Hence, to achieve greater depth of coverage for a proteome of interest, most groups routinely subfractionate the sample prior to LC-MS/MS so that the material entering LC-MS/MS is less complex than the original sample. Protein and/or peptide fractionation methods that biochemists have used for decades, such as strong cation exchange chromatography (SCX), isoelectric focusing (IEF) and SDS-PAGE, are the most common prefractionation methods used currently. There has, as yet, been no comprehensive, controlled evaluation of the relative merits of the various methods, although some binary comparisons have been made. Here, we compare the most popular methods for fractionating samples at both the protein and peptide level, replicating all analyses to provide estimates of the variability in the analyses and controlling precisely for instrument time dedicated to each analysis, as well as directly measuring the recovery of protein or peptide from each fractionation procedure. For maximal proteome coverage, SDS-PAGE is very clearly the most effective method tested, with more than 90% of the entire data set found. When considering the amount of material recovered after each fractionation procedure, solution-based IEF and SCX performed similarly, with approximately 80% of the input being recovered.
Increased capacity in an MS protection ringusing WDM technique and OADM:the ‘coloured section’ ring (1996)

The authors present a new method for upgrading the capacity of an existing SDH ring without having to either install additional rings or use higher bit rate equipment. The optimisation is obtained by assigning a specific wavelength to each multiplex section (MS) of the SDH ring. With wavelength routing new possibilities are provided in the network for addressing each node separately, with an order independent of the physical location.
Shuffled Iterative Decoding (2005)

Shuffled versions of iterative decoding of low-density parity-check codes and turbo codes are presented. The proposed schemes have about the same computational complexity as the standard versions, and converge faster. Simulations show that the new schedules offer better performance/complexity tradeoffs, especially when the maximum number of iterations has to remain small.
Pharmacokinetics, safety, and endocrine and appetite effects of ghrelin administration in young healthy subjects (2004)

These results suggest that ghrelin is safe, and that clinical trials may be started to assess the usefulness of ghrelin for the treatment of disorders related to GH secretion and appetite.
Reliable on-line human signature verification system for point-of-sales applications (2002)

Online dynamic signature verification systems were designed and tested. Data acquisition consisted of compiling a database of more than ten thousand signatures in (x(t), y(t))-form using a graphics tablet. For feature extraction we started with a 42-parameter feature set and advanced to a set of 49 normalized features. The normalized features tolerate inconsistencies in genuine signatures while retaining the power to discriminate against forgeries. For decision making we studied several classifiers types. Specifically, a modified versions of our so-called majority classifier yielded 2.5% equal error rate and, more importantly, an asymptotic performance of 7% false acceptance rate at zero false rejection rate using only 15 parameter features.
Analysis on properties of shale oil pyrolyzed from Huadian oil shale (2012)

Pyrolysis of oil shale was performed to produce shale oil. The effect of heating rates on the density, viscosity, solidification point, pour point, calorific value as well as distillation of shale oil was investigated. The results showed that the density of shale oil increased gradually with a rise of the heating rates. The solidification point and pour point increased, while increasing to some extent, then decreased. The shale oil obtained under 15°C/min has the highest solidification point and pour point values. The calorific value of shale oil decreased gradually. Shale oil was distillated at different heating rates, and the distillate yield of each temperature range was different. The main objective of this study is to characterize shale oils to lay the foundation for industrial production of shale oil in the future.
Increased Selectivity toward Cytoplasmic versus Mitochondrial Ribosome Confers Improved Efficiency of Synthetic Aminoglycosides in Fixing Damaged Genes: A Strategy for Treatment of Genetic Diseases Caused by Nonsense Mutations (2012)

Compelling evidence is now available that gentamicin and Geneticin (G418) can induce the mammalian ribosome to suppress disease-causing nonsense mutations and partially restore the expression of functional proteins. However, toxicity and relative lack of efficacy at subtoxic doses limit the use of gentamicin for suppression therapy. Although G418 exhibits the strongest activity, it is very cytotoxic even at low doses. We describe here the first systematic development of the novel aminoglycoside (S)-11 exhibiting similar in vitro and ex vivo activity to that of G418, while its cell toxicity is significantly lower than those of gentamicin and G418. Using a series of biochemical assays, we provide proof of principle that antibacterial activity and toxicity of aminoglycosides can be dissected from their suppression activity. The data further indicate that the increased specificity toward cytoplasmic ribosome correlates with the increased activity and that the decreased specificity toward mitochondrial ribosome confers the lowered cytotoxicity.
You Talking to Me? A Corpus and Algorithm for Conversation Disentanglement (2008)

When multiple conversations occur simultaneously, a listener must decide which conversation each utterance is part of in order to interpret and respond to it appropriately. We refer to this task as disentanglement. We present a corpus of Internet Relay Chat (IRC) dialogue in which the various conversations have been manually disentangled, and evaluate annotator reliability. This is, to our knowledge, the first such corpus for internet chat. We propose a graph-theoretic model for disentanglement, using discourse-based features which have not been previously applied to this task. The model’s predicted disentanglements are highly correlated with manual annotations.
Demonstration of highly efficient waveguiding in a photonic crystal slab at the 15-µm wavelength (2000)

Highly efficient transmission of 1.5-microm light in a two-dimensional (2D) photonic crystal slab waveguide is experimentally demonstrated. Light waves are shown to be guided along a triple-line defect formed within a 2D crystal and vertically by a strong index-guiding mechanism. At certain wavelength ranges, complete transmission is observed, suggesting lossless guiding along this photonic one-dimensional conduction channel.
Characterization of nerve growth factor precursor protein expression by human prostate stromal cells: A role in selective neurotrophin stimulation of prostate epithelial cell growth (1999)

BACKGROUND Nerve growth factor (NGF) immunoreactive proteins derived from human prostatic stromal cells (hPS) have been implicated in the paracrine regulation of prostate epithelial cell growth. However, mature NGFβ does not appear to be expressed by these cells. In order to determine whether NGF precursors are expressed by these cells, we investigated the potential processing and expression of precursor forms of NGF by human prostatic stromal cells, and examined the effects of NGF precursor moieties along with the other members of the neurotrophin family of gene products on soft agar colony formation of prostate epithelial cells. METHODS Specific antibodies to the peptide domains defined as N4 and L38, and the NGFβ moiety of prepro-NGF, were used in immunoblot assays to characterize the molecular weight forms of precursor NGF secreted by human prostatic stromal cells. The potential processing of NGF precursors with two enzymes, NGFγ and trypsin, was performed by incubation with stromal cell secretory protein containing precursor NGF. The selective effects of the N4, L38, and NGFβ peptide domains of precursor NGF, along with the remaining members of the neurotrophin family, brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4/5 (NT-4/5), were examined for their ability to stimulate growth of prostate tumor epithelial cells in an assay of soft agar colony formation. RESULTS Immunoblot analysis of stromal cell secretory protein identified NGF precursors of 35 kDa and 27 kDa, along with the partially processed 22-kDa form of pro-NGF, whereas mature NGFβ was not observed. Treatment of precursor NGF with NGFγ and trypsin did not produce the large intermediate forms of pro-NGF, although these two enzymes did appear to cleave the N-terminal peptide from NGFβ. Of the N4, L38, and NGFβ peptide domains of precursor NGF, only NGFβ significantly stimulated the anchorage-independent growth of TSU-pr1 prostate epithelial cells in soft agar. The other members of the neurotrophin family of gene products had no effect on the anchorage-independent growth of prostate tumor cells. CONCLUSIONS Human prostate stromal cells secrete the 35-kDa and 27-kDa precursor forms of NGF arising from alternate start sites, and the partially processed 22-kDa form of pro-NGF. Whereas the N4, L38, and NGFβ peptide domains present within pro-NGF were previously shown to induce phosphorylation of the high-affinity NGF receptor, tropomyosin receptor kinase (Trk), only the NGFβ moiety was able to stimulate anchorage-independent growth of prostate tumor cells. Likewise, the other neurotrophin family members did not stimulate anchorage-independent growth of prostate tumor cells. Hence, it would appear that NGF may be the predominant neurotrophic growth factor for prostate growth, albeit via precursor forms of NGF, and that its effect appears to be selectively mediated via the NGFβ moiety of these NGF precursors. Prostate 41:39–48, 1999. © 1999 Wiley-Liss, Inc.
Mebendazole Induces Apoptosis via Bcl-2 Inactivation in Chemoresistant Melanoma Cells (2008)

Most metastatic melanoma patients fail to respond to available therapy, underscoring the need for novel approaches to identify new effective treatments. In this study, we screened 2,000 compounds from the Spectrum Library at a concentration of 1 micromol/L using two chemoresistant melanoma cell lines (M-14 and SK-Mel-19) and a spontaneously immortalized, nontumorigenic melanocyte cell line (melan-a). We identified 10 compounds that inhibited the growth of the melanoma cells yet were largely nontoxic to melanocytes. Strikingly, 4 of the 10 compounds (mebendazole, albendazole, fenbendazole, and oxybendazole) are benzimidazoles, a class of structurally related, tubulin-disrupting drugs. Mebendazole was prioritized to further characterize its mechanism of melanoma growth inhibition based on its favorable pharmacokinetic profile. Our data reveal that mebendazole inhibits melanoma growth with an average IC(50) of 0.32 micromol/L and preferentially induces apoptosis in melanoma cells compared with melanocytes. The intrinsic apoptotic response is mediated through phosphorylation of Bcl-2, which occurs rapidly after treatment with mebendazole in melanoma cells but not in melanocytes. Phosphorylation of Bcl-2 in melanoma cells prevents its interaction with proapoptotic Bax, thereby promoting apoptosis. We further show that mebendazole-resistant melanocytes can be sensitized through reduction of Bcl-2 protein levels, showing the essential role of Bcl-2 in the cellular response to mebendazole-mediated tubulin disruption. Our results suggest that this screening approach is useful for identifying agents that show promise in the treatment of even chemoresistant melanoma and identifies mebendazole as a potent, melanoma-specific cytotoxic agent.
The Relationship between the Magnitude of the Specific Antibody Response to Experimental Salmonella enteritidis Infection in Laying Hens and Their Production of Contaminated Eggs (2001)

Detecting infected laying flocks is a vital part of many efforts to control egg-associated transmission of Salmonella enteritidis to humans. The relationship between the development of a specific antibody response in infected hens and the deposition of S. enteritidis in eggs is important for establishing the epidemiologic relevance of serologic testing methods. In two trials, laying hens were infected with large oral doses of phage types 13a and 14b isolates of S. enteritidis. Approximately 38% of all infected hens produced at least one contaminated egg, at an overall incidence of 5.2%, between 3 and 23 days postinoculation. As determined by enzyme-linked immunosorbent assay with an S. enteritidis flagellar antigen, 91.7% of inoculated hens produced specific serum antibodies. Although hens with very high antibody titers were associated with a significantly elevated frequency of egg contamination, a consistently direct relationship was not evident between the magnitude of the antibody responses of individual hens and the frequency at which they laid contaminated eggs. Accordingly, although serologic tests can be valuable screening tools for preliminary detection of S. enteritidis infections in poultry, the magnitude of the antibody responses detected in individual hens may not predict the overall risk of egg contamination associated with particular laying flocks.
Gram-negative bacteria account for main differences between faecal microbiota from patients with ulcerative colitis and healthy controls (2012)

Detailed knowledge about the composition of the intestinal microbiota may be critical to unravel the pathogenesis of ulcerative colitis (UC), a human chronic inflammatory bowel disease, since the intestinal microbes are expected to influence some of the key mechanisms involved in the inflammatory process of the gut mucosa. The aim of this study was to investigate the faecal microbiota in patients either with UC in remission (n=6) or with active disease (n=6), and in healthy controls (n=6). The composition of Gram-negative bacteria and Gram-positive bacteria was examined. Antigenic structures of Gram-negative bacteria such as lipopolysaccharides have been related to the inflammatory responses and pathogenesis of inflammatory bowel disease. Dice cluster analysis and principal component analysis of faecal microbiota profiles obtained by denaturing gradient gel electrophoresis and quantitative PCR, respectively, revealed that the composition of faecal bacteria from UC patients with active disease differed from the healthy controls and that this difference should be ascribed to Gram-negative bacteria. The analysis did not show any clear grouping of UC patients in remission. Even with the relatively low number of subjects in each group, we were able to detect a statistically significant underrepresentation of Lactobacillus spp. and Akkermansia muciniphila in UC patients with clinically active disease compared to the healthy controls. In line with previous communications, we have shown that the microbiota in UC patients with active disease differ from that in healthy controls. Our findings indicate that alterations in the composition of the Gram-negative bacterial population, as well as reduced numbers of lactobacilli and A. muciniphila may play a role in UC.
Monoclonal antibodies against GARP/TGF-β1 complexes inhibit the immunosuppressive activity of human regulatory T cells in vivo (2015)

Regulatory T cells (Tregs) are essential to prevent autoimmunity, but excessive Treg function contributes to cancer progression by inhibiting antitumor immune responses. Tregs exert contact-dependent inhibition of immune cells through the production of active transforming growth factor-β1 (TGF-β1). On the Treg cell surface, TGF-β1 is in an inactive form bound to membrane protein GARP and then activated by an unknown mechanism. We demonstrate that GARP is involved in this activation mechanism. Two anti-GARP monoclonal antibodies were generated that block the production of active TGF-β1 by human Tregs. These antibodies recognize a conformational epitope that requires amino acids GARP137-139 within GARP/TGF-β1 complexes. A variety of antibodies recognizing other GARP epitopes did not block active TGF-β1 production by Tregs. In a model of xenogeneic graft-versus-host disease in NSG mice, the blocking antibodies inhibited the immunosuppressive activity of human Tregs. These antibodies may serve as therapeutic tools to boost immune responses to infection or cancer via a mechanism of action distinct from that of currently available immunomodulatory antibodies. Used alone or in combination with tumor vaccines or antibodies targeting the CTLA4 or PD1/PD-L1 pathways, blocking anti-GARP antibodies may improve the efficiency of cancer immunotherapy.
Recent advances in dielectric-resonator antenna technology (1998)

This paper features some of the advances in dielectric-resonator antenna technology at the Communications Research Centre. Several novel elements are presented that offer significant enhancements to parameters such as impedance bandwidth, circular-polarization bandwidth, gain, or coupling to various feed structures. Several linear and planar arrays are also presented, to illustrate the performance of dielectric-resonator antenna elements in the array environment.
Development of potent in vivo mutagenesis plasmids with broad mutational spectra (2015)

Methods to enhance random mutagenesis in cells offer advantages over in vitro mutagenesis, but current in vivo methods suffer from a lack of control, genomic instability, low efficiency and narrow mutational spectra. Using a mechanism-driven approach, we created a potent, inducible, broad-spectrum and vector-based mutagenesis system in E. coli that enhances mutation 322,000-fold over basal levels, surpassing the mutational efficiency and spectra of widely used in vivo and in vitro methods. We demonstrate that this system can be used to evolve antibiotic resistance in wild-type E. coli in <24 h, outperforming chemical mutagens, ultraviolet light and the mutator strain XL1-Red under similar conditions. This system also enables the continuous evolution of T7 RNA polymerase variants capable of initiating transcription using the T3 promoter in <10 h. Our findings enable broad-spectrum mutagenesis of chromosomes, episomes and viruses in vivo, and are applicable to both bacterial and bacteriophage-mediated laboratory evolution platforms.
A tree reconstruction method that is economical in the number of pairwise comparisons used. (1989)

A fast method for reconstructing phylogenies from distance data is presented. The method is economical in the number of pairwise comparisons needed. It can be combined with a new phylogenetic alignment procedure to yield an algorithm that gives a complete history of a set of homologous sequences. The method is applicable to very large distance matrices. An auxiliary program was developed that simplifies large phylogenies without ignoring biologically essential features. A set of 213 globins from vertebrates, plants, and Vitreoscilla (a prokaryote) were analyzed using this method.
Asymptotic formalism for ultraflat optical frequency comb generation using a Mach-Zehnder modulator (2007)

We theoretically prove that a conventional Mach-Zehnder modulator can generate an optical frequency comb with excellent spectral flatness. The modulator is asymmetrically dual driven by large amplitude sinusoidal signals with different amplitudes. The driving condition to obtain spectral flatness is analytically derived and optimized, yielding a simple formula. This formula also predicts the conversion efficiency and bandwidth of the generated frequency comb.
Apple polyphenols and cardiovascular disease - a review of the evidence (2010)

A diet high in fruits and vegetables has been associated with a lower risk of some diseases, including cardiovascular disease. Besides food constituents, such as fibre or beta-carotene, other bioactive plant compounds such as polyphenols have been suggested to contribute to this protective effect. Apples are one of the most popular fruits in the UK, and apples and apple products, such as fruit juices and apple purées, contribute to the total polyphenol intake of the UK population, although data on the extent of their contribution are not available. The aim of this review was to summarise the evidence available from human studies on the effect of polyphenols found in apples on cardiovascular risk factors, including blood lipids and blood pressure. The literature search comprised randomised clinical trials carried out in humans using either apples or apple products, or other foods or supplements containing a significant amount of one or more polyphenols present in apples. Our search showed that there is very limited evidence available from human studies. Preliminary findings show that polyphenols present in apples may potentially have a positive influence on blood lipid parameters and blood pressure in humans. However, firm conclusions cannot be made based on the limited studies available. Further research is needed to evaluate the full potential of polyphenols and their effect on human health.
Suppression of basic fibroblast growth factor expression by antisense oligodeoxynucleotides inhibits the growth of transformed human astrocytes. (1991)

Basic fibroblast growth factor (bFGF) is a heparin-binding protein expressing potent mitogenic and angiogenic properties. Elevated levels of bFGF have recently been described in human glioma cell lines. The high degree of vascularity and invasiveness which characterize human gliomas suggest that activated expression of bFGF or similar proteins may be related to the aberrant growth patterns of these tumors. The influence of endogenous bFGF on glioma cell growth in vitro was evaluated in the present study by down-regulating bFGF expression using antisense oligonucleotide primers. The addition of 50 microM bFGF-specific antisense primer to the human glioma cell line SNB-19 resulted in an 80% inhibition in glioma growth. This effect was saturable and specific. Antisense primers directed to two different sites of bFGF mRNA were effective in suppressing SNB-19 growth, whereas sense strand primer was ineffective. Furthermore, only the antisense primer significantly reduced the specific activity of bFGF protein in SNB-19 cell extracts. Neither antisense or sense primers inhibited the growth of non-transformed human glia. bFGF mRNA was detected in both transformed and non-transformed human glia by polymerase chain reaction analysis suggesting that alterations in bFGF isoform content or activity may be specifically related to abnormal growth control in human gliomas.