gebhart/patrepeval huggingface dataset:
A New Approach to Drug Therapy: Fc-Fusion Technology (2017)

Fc-fusion proteins have been successfully implemented in the treatment of many diseases. Advances in engineering and design of these therapeutic proteins have helped prolong the drug half-life, which in turn allows for longer dosing intervals (i.e. weekly or bi-weekly administration) and, thus, may improve patient adherence in a real world setting. In this review, we provide a brief summary of half-life extension technologies. Here, we focus on IgG-Fc fusion and the key roles that the Fc fragment plays in both physiology and drug therapy, and the potential to elicit immune responses in humans. This review provides examples of various recombinant Fc-fusion protein drugs, including, etanercept (Enbrel®) for the treatment of various forms of arthritis, aflibercept (Eylea®), for the treatment of neovascular age-related macular degeneration and dulaglutide (Trulicity™) for the treatment of type 2 diabetes. All of these fusion proteins can be administered at least weekly. Overall, Fc-fusion proteins have proven to be a successful alternative to improve pharmacological properties of therapeutic drugs, with more convenient utilization in the real world and with low immunogenic potential.
Ultraviolet laser‐induced fluorescence of colonic tissue: Basic biology and diagnostic potential (1992)

Laser-induced fluorescence (LIF) of colonic tissue was examined both in vitro and in vivo to assess the ability of the technique to distinguish neoplastic from hyperplastic and normal tissue and to relate the LIF spectra to specific constituents of the colon. Spectra from 86 normal colonic sites, 35 hyperplastic polyps, 49 adenomatous polyps, and 7 adenocarcinomas were recorded both in vivo and in vitro. With 337-nm excitation, the fluorescence spectra all had peaks at 390 and 460 nm, believed to arise from collagen and NADH, and a minimum at 425 nm, consistent with absorption attributable to hemoglobin. The spectra of colonic tissue recorded both in vivo and in vitro are different, primarily in the NADH fluorescence component, which decays exponentially with time after resection. When normal colonic tissue is compared to hyperplastic or adenomatous polyps, the predominant changes in the fluorescence spectra are a decrease in collagen fluorescence and a slight increase in hemoglobin reabsorption. A multivariate linear regression (MVLR) analysis was used to distinguish neoplastic tissue from non-neoplastic tissue with a sensitivity, specificity, predictive value positive, and predictive value negative toward neoplastic tissue of 80%, 92%, 82%, and 91%, respectively. When the MVLR technique was used to distinguish neoplastic polyps from non-neoplastic polyps, values of 86%, 77%, 86%, and 77% respectively, were obtained. The data suggest that the LIF measurements sense changes in polyp morphology, rather than changes in fluorophores specific to polyps, and it is this change in morphology that leads indirectly to discrimination of polyps.
In vivo regulation of peripheral-type benzodiazepine receptor and glucocorticoid synthesis by Ginkgo biloba extract EGb 761 and isolated ginkgolides. (1996)

Glucocorticoid excess has broad pathogenic potential including neurotoxicity, neuroendangerment, and immunosuppression. Glucocorticoid synthesis is regulated by ACTH, which acts by accelerating the transport of the precursor cholesterol to the mitochondria where steroidogenesis begins. Ginkgo biloba is one of the most ancient trees, and extracts from its leaves have been used in traditional medicine. A standardized extract of Ginkgo biloba leaves, termed EGb 761 (EGb), has been shown to have neuroprotective and antistress effects. In vivo treatment of rats with EGb, and its bioactive components ginkgolide A and B, specifically reduces the ligand binding capacity, protein, and messenger RNA expression of the adrenocortical mitochondrial peripheral-type benzodiazepine receptor (PBR), a key element in the regulation of cholesterol transport, resulting in decreased corticosteroid synthesis. As expected, the ginkgolide-induced decrease in glucocorticoid levels resulted in increased ACTH release, which in turn induced the expression of the steroidogenic acute regulatory protein. Because ginkgolides reduced the adrenal PBR expression and corticosterone synthesis despite the presence of high levels of steroidogenic acute regulatory protein, these data demonstrate that PBR is indispensable for normal adrenal function. In addition, these results suggest that manipulation of PBR expression could control circulating glucocorticoid levels, and that the antistress and neuroprotective effects of EGb are caused by to its effect on glucocorticoid biosynthesis.
Amelioration of joint disease in a rat model of collagen‐induced arthritis by M40403, a superoxide dismutase mimetic (2001)

This study shows that a low molecular weight mimetic of SOD, M40403, attenuates the degree of chronic inflammation, tissue damage, and bone damage associated with CIA in the rat, and supports the possible use of SOD mimetics as therapeutic agents for the management of chronic diseases such as rheumatoid arthritis.
Structure of the human liver/bone/kidney alkaline phosphatase gene. (1988)

In man, there are multiple forms of alkaline phosphatase encoded by at least three homologous genes: placental, intestinal, and liver/bone/kidney. This report describes the characterization of the human liver/bone/kidney alkaline phosphatase locus. The gene appears to exist as a single copy in the haploid genome and is comprised of 12 exons distributed over more than 50 kilobases. In liver, kidney, SAOS-2 human osteosarcoma cells, and cultured fibroblasts, there is a single major start for transcription situated about 25 nucleotides downstream of an A/T-rich motif. The promoter region is extremely G/C-rich, is relatively abundant in the dinucleotide CpG, and contains four copies of the consensus sequence for SP1 binding (GGGCGG). The liver/bone/kidney alkaline phosphatase gene is at least five times larger than the intestinal and placental alkaline phosphatase genes, mainly due to intron size differences. Intron-exon junctions occur at analogous positions in all three genes, but there is an extra non-coding exon at the 5' end of the liver/bone/kidney alkaline phosphatase gene. The relevance of our findings with respect to the evolution of the human alkaline phosphatase multigene family is discussed.
Crystal Structure of Defensin HNP-3, an Amphiphilic Dimer: Mechanisms of Membrane Permeabilization (1991)

Defensins (molecular weight 3500 to 4000) act in the mammalian immune response by permeabilizing the plasma membranes of a broad spectrum of target organisms, including bacteria, fungi, and enveloped viruses. The high-resolution crystal structure of defensin HNP-3 (1.9 angstrom resolution, R factor 0.19) reveals a dimeric beta sheet that has an architecture very different from other lytic peptides. The dimeric assembly suggests mechanisms by which defensins might bind to and permeabilize the lipid bilayer.
Whole-Genome DNA Microarray Analysis of a Hyperthermophile and an Archaeon: Pyrococcus furiosus Grown on Carbohydrates or Peptides (2003)

The first complete-genome DNA microarray was constructed for a hyperthermophile or a nonhalophilic archaeon by using the 2,065 open reading frames (ORFs) that have been annotated in the genome of Pyrococcus furiosus (optimal growth temperature, 100 degrees C). This was used to determine relative transcript levels in cells grown at 95 degrees C with either peptides or a carbohydrate (maltose) used as the primary carbon source. Approximately 20% (398 of 2065) of the ORFs did not appear to be significantly expressed under either growth condition. Of the remaining 1,667 ORFs, the expression of 125 of them (8%) differed by more than fivefold between the two cultures, and 82 of the 125 (65%) appear to be part of operons, indicating extensive coordinate regulation. Of the 27 operons that are regulated, 5 of them encode (conserved) hypothetical proteins. A total of 18 operons are up-regulated (greater than fivefold) in maltose-grown cells, including those responsible for maltose transport and for the biosynthesis of 12 amino acids, of ornithine, and of citric acid cycle intermediate products. A total of nine operons are up-regulated (greater than fivefold) in peptide-grown cells, including those encoding enzymes involved in the production of acyl and aryl acids and 2-ketoacids, which are used for energy conservation. Analyses of the spent growth media confirmed the production of branched-chain and aromatic acids during growth on peptides. In addition, six nonlinked enzymes in the pathways of sugar metabolism were regulated more than fivefold--three in maltose-grown cells that are unique to the unusual glycolytic pathway and three in peptide-grown cells that are unique to gluconeogenesis. The catalytic activities of 16 metabolic enzymes whose expression appeared to be highly regulated in the two cell types correlated very well with the microarray data. The degree of coordinate regulation revealed by the microarray data was unanticipated and shows that P. furiosus can readily adapt to a change in its primary carbon source.
Ultra high quality factor one dimensional photonic crystal/photonic wire micro-cavities in silicon-on-insulator (SOI) (2008)

We present experimental results on photonic crystal/photonic wire micro-cavity structures that demonstrate further enhancement of the quality-factor (Q-factor)--up to approximately 149,000--in the fibre telecommunications wavelength range. The Q-values and the useful transmission levels achieved are due, in particular, to the combination of both tapering within and outside the micro-cavity, with carefully designed hole diameters and non-periodic hole placement within the tapered section. Our 2D Finite Difference Time Domain (FDTD) simulation approach shows good agreement with the experimental results.
Prevalence of a History of Skin Cancer in 2007 (2010)

My incidence-based model indicates that the prevalence of a skin cancer history is about 5 times higher than that of breast or prostate cancer and greater than the 31-year prevalence of all other cancers combined. Despite their high frequency, population-based incidence and burden data for BSC and SCC are largely lacking.
Policy Capturing LP for Ranged Ratings in Performance Appraisal (2003)

For inferring criteria in a performance appraisal, linear programming (LP) has been utilized as an alternative to policy capturing (PC). Previous policy capturing LP (PCLP) studies were limited to the criteria of exact numerical ratings. However. under certain evaluation 
circumstances. a ranged rating with a lower and upper bound may be preferred over an exact numerical value. Therefore, this study introduces a new LP model that allows ranged ratings. A simple example is given to illustrate our model.
Allogeneic CAR-T Cells: More than Ease of Access? (2018)

Patient derived anti-CD19 chimeric antigen receptor-T (CAR-T) cells are a powerful tool in achieving a complete remission in a range of B-cell malignancies, most notably B-acute lymphoblastic leukaemia (B-ALL) and diffuse large B-cell lymphoma (DLBCL). However, there are limitations, including inability to manufacture CAR-T cells from the patient's own T cells, disease progression and death prior to return of engineered cells. T cell dysfunction is known to occur in cancer patients, and several groups have recently described differences in CAR-T cells generated from chronic lymphocytic leukaemia (CLL) patients compared with those from a healthy donor. This is thought to contribute to the low response rate in this disease group. Healthy donor, gene-edited CAR-T cells which do not require human leucocyte antigen (HLA) matching have the potential to provide an 'off the shelf' product, overcoming the manufacturing difficulties of producing CAR-T cells for each individual patient. They may also provide a more functional, potent product for malignancies such as CLL, where T cell dysfunction is common and frequently cannot be fully reversed during the manufacturing process. Here we review the potential benefits and obstacles for healthy donor, allogeneic CAR-T cells.
Tolerization as a tool for generating novel monoclonal antibodies (2002)

Standard hybridoma production involves the fusion of spleen cells from an immunized mouse with a non-secretory murine myeloma cell line. While this technology has provided numerous reagents that are highly valuable, demand is now increasing for monoclonal antibodies which can distinguish between closely related antigens. Induction of tolerance towards common antigens enables the recovery of high-specificity reagents that have previously proved elusive. This review details a number of strategies using either complex protein mixtures or purified proteins as tolerogens and subsequent immunization with a closely related immunogen.
VEGF-Induced Retinal Angiogenic Signaling Is Critically Dependent on Ca2+Signaling by Ca2+/Calmodulin-Dependent Protein Kinase II (2011)

VEGF increases [Ca(2+)](i) in BRECs through activation of the PLC-IP(3) signal transduction pathway. VEGF-induced phosphorylation of the proangiogenic protein Akt is critically dependent on this increase in [Ca(2+)](i) and the subsequent activation of CaMKII. Pharmacologic inhibition of Ca(2+)-mediated signaling in retinal endothelial cells blocks VEGF-induced angiogenic responses. These results suggest that the PLC/IP(3)/Ca(2+)/CaMKII signaling pathway may be a rational target for the treatment of angiogenesis-related disorders of the eye.
Inflammatory responses and coronary heart disease (1998)

The “dirty chicken” hypothesis was proposed by Solomons to explain why children reared in poverty, though appearing healthy and receiving adequate nutrition, end up as short adults.1 Based on the observation that antibiotic supplementation reverses poor growth in chickens reared in overcrowded unhygienic conditions, he suggested that chronic subclinical infection induces a low grade systemic inflammation and that this produces a qualitatively similar effect to full blown acute inflammation—that is, chronic anorexia and increased basal metabolic rate, with cytokines being the mediators. What does this have to do with humans reared in relatively overcrowded unhygienic conditions and cardiovascular disease?

There is an increasing interest in the relation between chronic low grade systemic inflammation, as indicated by serum levels of C reactive protein, and mortality from coronary heart disease. 2 3 There has, however, been little knowledge of the determinants of this response and its importance in the pathogenesis of atherosclerosis. Chronic subclinical infection with Chlamydia pneumoniae , Helicobacter pylori , chronic bronchitis, and chronic dental sepsis have been associated with raised values of C reactive protein within the normal range3 and have been implicated …
Prostate-specific antigen (PSA) promoter-driven androgen-inducible expression of sodium iodide symporter in prostate cancer cell lines. (1999)

Currently, no curative therapy for metastatic prostate cancer exists. Causing prostate cancer cells to express functionally active sodium iodide symporter (NIS) would enable those cells to concentrate iodide from plasma and might offer the ability to treat prostate cancer with radioiodine. Therefore, the aim of our study was to achieve tissue-specific expression of full-length human NIS (hNIS) cDNA in the androgen-sensitive human prostatic adenocarcinoma cell line LNCaP and in subcell lines C4, C4-2, and C4-2b in vitro. For this purpose, an expression vector was generated in which full-length hNIS cDNA coupled to the prostate-specific antigen (PSA) promoter has been ligated into the pEGFP-1 vector (NIS/PSA-pEGFP-1). The PSA promoter is responsible for androgen-dependent expression of PSA in benign and malignant prostate cells and was therefore used to mediate androgen-dependent prostate-specific expression of NIS. In addition, two control vectors were designed, which consist of the pEGFP-1 vector containing the PSA promoter without NIS cDNA (PSA-pEGFP-1) and NIS cDNA without the PSA promoter (NIS-pEGFP-1). Prostate cancer cells were transiently transfected with each of the above-described expression vectors, incubated with or without androgen (mibolerone) for 48 h, and monitored for iodide uptake activity. In addition, stably transfected LNCaP cell lines were established for each vector. Prostate cells transfected with NIS/PSA-pEGFP-1 showed perchlorate-sensitive, androgen-dependent iodide uptake in a range comparable to that observed in control cell lines transfected with hNIS cDNA. Perchlorate-sensitive iodide uptake was not observed in cells transfected with NIS/PSA-pEGFP-1 and treated without androgen or in cells transfected with the control vectors. In addition, prostate cancer cell lines without PSA expression (PC-3 and DU-145) did not show iodide uptake activity when transfected with NIS/PSA-pEGFP-1. Western blotting of LNCaP and C4-2b cell membranes transfected with NIS/PSA-pEGFP-1 using a monoclonal antibody that recognizes the COOH-terminus of hNIS revealed a band with a molecular weight of 90,000 that was not detected in androgen-deprived cells or in cells transfected with the control vectors, as well as a minor band at Mr 150,000 in transiently transfected LNCaP cell membranes. In conclusion, tissue-specific androgen-dependent iodide uptake activity has been induced in prostate cancer cells by PSA promoter-directed NIS expression. This study represents an initial step toward therapy of prostate cancer with radioiodine.
A Genetic Linkage Map of the Mouse: Current Applications and Future Prospects (1993)

Technological advances have made possible the development of high-resolution genetic linkage maps for the mouse. These maps in turn offer exciting prospects for understanding mammalian genome evolution through comparative mapping, for developing mouse models of human disease, and for identifying the function of all genes in the organism.
Studying the mechanism of CD47–SIRPα interactions on red blood cells by single molecule force spectroscopy (2014)

The interaction forces and binding kinetics between SIRPα and CD47 were investigated by single-molecule force spectroscopy (SMFS) on both fresh and experimentally aged human red blood cells (hRBCs). We found that CD47 experienced a conformation change after oxidation, which influenced the interaction force and the position of the energy barrier between SIRPα and CD47. Our results are significant for understanding the mechanism of phagocytosis of red blood cells at the single molecule level.
Bipotential glial precursor cells of the optic nerve express the NG2 proteoglycan (1987)

We have studied the expression of the NG2 chondroitin sulfate proteoglycan on bipotential glial precursor cells in cultures of postnatal rat optic nerve. Purified populations of these precursor cells were prepared by panning dissociated optic nerve cells on dishes coated with monoclonal A2B5 antibody. Using immunofluorescence double staining, we found that NG2 was present on almost 95% of the purified A2B5+ precursor cells. The NG2 core protein from optic nerve cells was identified by immune precipitation and PAGE and was found to be identical to the 300,000 Da NG2 core protein from a clonal rat cell line B49. Over a culture period of 5 d in medium containing 10% fetal calf serum, more than 80% of the NG2+ precursor cells acquired the glial fibrillary acidic protein (GFAP), an astrocyte-specific marker. Under these conditions, fewer than 10% of the NG2+ cells expressed galactocerebroside (GC), an oligodendrocyte-specific marker. These GFAP+GC- type II astrocytes continued to express the NG2 antigen for up to 10 d in culture. During a 5 d culture period in hormonally supplemented, serum-free medium, fewer than 15% of the NG2+ cells expressed GFAP, while up to 40% expressed GC. The NG2 antigen continued to be expressed for only a short period of time by these GFAP-GC+ oligodendrocytes, so that mature oligodendrocytes in the cultures became NG2-. These results support our previous suggestion that the NG2 antigen is found on a class of neural cells that can differentiate along more than one pathway.
Metabolomics and biochemical profiling in drug discovery and development. (2002)

Metabolomics brings a different and complementary perspective to biomedical research and therapeutic development. Metabolites are measurable, directly responsible for health, and changeable through intervention. By definition, the concentrations of metabolites are the direct reflection of metabolism, and by measuring changes in metabolite concentrations, the full range of biochemical effects induced by a therapeutic intervention can be determined. In a clinical setting, metabolomics can be used to diagnose or predict disease, stratify patient populations by their specific metabolism, or to determine the safety or efficacy of a therapeutic intervention. Metabolomics is useful in virtually all aspects of biomedical research, and it is likely to evolve into an essential component of the drug discovery and development process.
Engineering an enzyme by site-directed mutagenesis to be resistant to chemical oxidation. (1985)

Site-directed mutagenesis can be employed to alter activity critical residues in proteins which are susceptible to chemical oxidation. Previous studies have implicated methionine 222 as a primary site for oxidative inactivation of subtilisin (Stauffer, C. E., and Etson, D. (1969) J. Biol. Chem. 244, 5333-5338). Because of uncertainties in predicting which amino acid would be the optimal substitute for methionine 222, we prepared all 19 amino acid substitutions at this site in the cloned subtilisin gene using a cassette mutagenesis method (Wells, J. A., Vasser, M., and Powers, D. P. (1985) Gene (Amst.), in press). Mutant enzymes were expressed in Bacillus subtilis and were found to vary widely in specific activity. Mutants containing nonoxidizable amino acids (i.e. Ser, Ala, and Leu) were resistant to inactivation by 1 M H2O2, whereas methionine and cysteine enzymes were rapidly inactivated. These studies demonstrate the feasibility of improving oxidative stability in proteins by site-directed mutagenesis.
Preoperative Chemotherapy in Primary Operable Breast Cancer: Results From the European Organization for Research and Treatment of Cancer Trial 10902 (2001)

The use of preoperative chemotherapy yields similar results in terms of PFS, OS, and locoregional control compared with conventional postoperative chemotherapy. In addition, preoperative chemotherapy enables more patients to be treated with breast-conserving surgery. Because preoperative chemotherapy does not improve disease outcome compared with postoperative chemotherapy, future trials should involve quality-of-life studies to investigate whether patients will benefit from this treatment modality.
Orientation radiograms for image retrieval: an alternative to segmentation (1996)

For content based image retrieval using shape descriptors, most approaches so far extract shape information from a segmentation of the image. Shape features derived based on a specific segmentation are not suitable for images containing complex structures. Further, static segmentation based approaches are useful only for a small set of queries. In this paper we discuss the limitations of such boundary based shape features, and propose an alternative shape characterization technique based on orientation radiograms. A working image retrieval system based on this approach is described and sample results are presented for a full-image query.