gebhart/patrepeval huggingface dataset:
Gla-Containing Proteins of Bone (1989)

Bone has high levels of two proteins which contain the vitamin K-dependent Ca2+ binding amino acid, gamma-carboxyglutamic acid (Gla). Bone Gla protein (BGP, osteocalcin) is a 49 residue water soluble protein and matrix Gla protein (MGP) is a 79 residue water insoluble protein. BGP is synthesized only by calcified tissues while MGP is synthesized by calcified tissues, cartilage, and all soft tissues tested. The synthesis of both proteins in osteoblastic cells is stimulated by 1,25(OH)2D3. Treatment of rats with the vitamin K antagonist Warfarin causes secretion of a non-gamma-carboxylated BGP which cannot bind to hydroxyapatite. Warfarin treatment reduces bone levels of BGP to 2% of normal, but does not appear to affect the structure of bone. The only abnormality seen in rats treated with Warfarin is the mineralization of several cartilages. The pattern of cartilage calcification is similar to that seen in the fetal Warfarin syndrome in humans, and may be due to abnormal synthesis of MGP.
C constant: New concept for ray tracing–assisted intraocular lens power calculation (2014)

The C constant is a promising concept for ray tracing-assisted IOL power calculation.
Capsule endoscopy in clinical practice: concise up-to-date overview (2009)

Until recently, the small bowel was considered a 'no man's land' as the imaging modalities available for its investigation were laborious, invasive, costly, or involve significant radiation exposure. Wireless capsule endoscopy (WCE) has changed the field dramatically, over the last eight years. The established indications for small bowel WCE are obscure gastrointestinal bleed/anemia, Crohn's disease, hereditary polyposis syndromes, and to a lesser extent, evaluation of side effects of nonsteroidal anti-inflammatory medications and coeliac disease. We herein present an overview of the capsule examination, which seems to be a quickly improving area.
Properties of Sustained-Release Tablets Prepared by Hot-Melt Extrusion (1999)

The objectives of the present study were to investigate the properties of polyethylene oxide (PEO) as a drug carrier and to study the release mechanism of chlorpheniramine maleate (CPM) from matrix tablets prepared by hot-melt extrusion. During the hot-melt extrusion process, a dry powder blend of drug, polymer, and other adjuvants was fed into the extruder and melted inside the barrel of the machine. The molten mass was extruded through a rod-shaped die and then cut manually into 400-mg tablets. CPM and PEO were shown to be stable under the processing conditions. The molecular weight of the PEO, the drug loading percentage, and the inclusion of polyethylene glycol as a processing aid, were all found to influence the processing conditions and the drug release properties of the extruded tablets. Faster release of CPM from the matrix tablets was observed in acidic medium than in purified water and phosphate buffer (pH 7.4). Drug release from the matrix tablet was controlled by erosion of the PEO matrix and the diffusion of the drug through the swollen gel layer at the surface of the tablets. CPM was dispersed at the molecular level in the PEO matrix at low drug loading level and recrystallization of CPM was observed at high drug loading levels. Hot-melt extrusion was demonstrated to be a viable novel method to prepare sustained-release tablets. PEO was shown to be a suitable polymeric carrier for this process.
CAT‐1‐mediated arginine uptake and regulation of nitric oxide synthases for the survival of human breast cancer cell lines (2011)

Growth of the human MCF-7 breast cancer cell line is highly dependent on L-arginine. We have reported that L-arginine, released from extracellular substrates by prolactin (PRL)- and 17β-estradiol (E2)-induced carboxypeptidase-D in the cell membrane, promotes nitric oxide (NO) production for MCF-7 cell survival. Arginine uptake is mediated by members of the cationic amino acid transporter (CAT) family and may coincide with induction of nitric oxide synthase (NOS) for the production of NO. The present study investigated the CAT isoforms and PRL/E2 regulation of CAT and NOS in breast cancer cell lines. Using RT-PCR analysis, CAT-1, CAT-2A, and CAT-2B transcripts were detected in MCF-7, T47D, and MDA-MB-231 cells. The CAT-4 transcript was detected in MDA-MB-231 only. CAT-3 was not detected in any of these cells. PRL and E2 did not significantly alter levels of CAT-1 mRNA and protein, nor CAT-2A and CAT-2B mRNAs in MCF-7 and T47D cells. PRL and E2 also had no effect on the overall uptake of L-[2,3,4,5-H(3)] arginine into these cells. However, confocal immunofluorescent microscopy showed that PRL and E2 upregulated eNOS and iNOS proteins, which distributed in the cytoplasm and/or nucleus of MCF-7 cells. Knockdown of CAT-1 gene expression using small interfering RNA significantly decreased L-[2,3,4,5-H(3)]-arginine uptake, decreased viability and increased apoptosis of MCF-7 and T47D cells. In summary, several CAT isoforms are expressed in breast cancer cells. The CAT-1 isoform plays a role in arginine uptake and, together with PRL/E2-induced NOS, contribute to NO production for the survival of MCF-7 and T47D cells.
Increased Expression of Interleukin 23 p19 and p40 in Lesional Skin of Patients with Psoriasis Vulgaris (2004)

Psoriasis is a type I-deviated disease characterized by the presence of interferon (IFN)-gamma and multiple IFN-related inflammatory genes in lesions. Because interleukin (IL)-23 is now recognized to play a role in the recruitment of inflammatory cells in a T helper cell (Th)1-mediated disease, we examined psoriasis skin lesions for production of this newly described cytokine. IL-23 is composed of two subunits: a unique p19 subunit and a p40 subunit shared with IL-12. We found a reliable increase in p19 mRNA by quantitative reverse transcription polymerase chain reaction in lesional skin compared with nonlesional skin (22.3-fold increase; P = 0.001). The p40 subunit, shared by IL-12 and IL-23, increased by 11.6-fold compared with nonlesional skin (P = 0.003), but the IL-12 p35 subunit was not increased in lesional skin. IL-23 was expressed mainly by dermal cells and increased p40 immunoreactivity was visualized in large dermal cells in the lesions. Cell isolation experiments from psoriatic tissue showed strong expression of p19 mRNA in cells expressing monocyte (CD14+ CD11c+ CD83-) and mature dendritic cell (DC) markers (CD14- CD11c+ CD83+), whereas in culture, the mRNAs for p40 and p19 were strongly up-regulated in stimulated monocytes and monocyte-derived DCs, persisting in the latter for much longer periods than IL-12. Our data suggest that IL-23 is playing a more dominant role than IL-12 in psoriasis, a Th1 type of human inflammatory disease.
Tumor Suppressor P53 Binding Protein 1 (53bp1) Is Involved in DNA Damage–Signaling Pathways (2001)

The tumor suppressor p53 binding protein 1 (53BP1) binds to the DNA-binding domain of p53 and enhances p53-mediated transcriptional activation. 53BP1 contains two breast cancer susceptibility gene 1 COOH terminus (BRCT) motifs, which are present in several proteins involved in DNA repair and/or DNA damage-signaling pathways. Thus, we investigated the potential role of 53BP1 in DNA damage-signaling pathways. Here, we report that 53BP1 becomes hyperphosphorylated and forms discrete nuclear foci in response to DNA damage. These foci colocalize at all time points with phosphorylated H2AX (gamma-H2AX), which has been previously demonstrated to localize at sites of DNA strand breaks. 53BP1 foci formation is not restricted to gamma-radiation but is also detected in response to UV radiation as well as hydroxyurea, camptothecin, etoposide, and methylmethanesulfonate treatment. Several observations suggest that 53BP1 is regulated by ataxia telangiectasia mutated (ATM) after DNA damage. First, ATM-deficient cells show no 53BP1 hyperphosphorylation and reduced 53BP1 foci formation in response to gamma-radiation compared with cells expressing wild-type ATM. Second, wortmannin treatment strongly inhibits gamma-radiation-induced hyperphosphorylation and foci formation of 53BP1. Third, 53BP1 is readily phosphorylated by ATM in vitro. Taken together, these results suggest that 53BP1 is an ATM substrate that is involved early in the DNA damage-signaling pathways in mammalian cells.
Early Visual Concept Learning with Unsupervised Deep Learning (2016)

Automated discovery of early visual concepts from raw image data is a major open challenge in AI research. Addressing this problem, we propose an unsupervised approach for learning disentangled representations of the underlying factors of variation. We draw inspiration from neuroscience, and show how this can be achieved in an unsupervised generative model by applying the same learning pressures as have been suggested to act in the ventral visual stream in the brain. By enforcing redundancy reduction, encouraging statistical independence, and exposure to data with transform continuities analogous to those to which human infants are exposed, we obtain a variational autoencoder (VAE) framework capable of learning disentangled factors. Our approach makes few assumptions and works well across a wide variety of datasets. Furthermore, our solution has useful emergent properties, such as zero-shot inference and an intuitive understanding of "objectness".
Antibody and T cell responses of patients with adenocarcinoma immunized with mannan-MUC1 fusion protein. (1997)

Mucin 1 (MUC1) is a large complex glycoprotein that is highly expressed in breast cancer, and as such could be a target for immunotherapy. In mice, human MUC1 is highly immunogenic, particularly when conjugated to mannan, where a high frequency of CD8(+) MHC-restricted cytotoxic T lymphocytes is induced, accompanied by tumor protection. On this basis, a clinical trial was performed in which 25 patients with advanced metastatic carcinoma of breast, colon, stomach, or rectum received mannan-MUC1 in increasing doses. After 4 to 8 injections, large amounts of IgG1 anti-MUC1 antibodies were produced in 13 out of 25 patients (with antibody titers by ELISA of 1/320-1/20,480). Most of the antibodies reacted to the epitopes STAPPAHG and PAPGSTAP. In addition, T cell proliferation was found in 4 out of 15 patients, and CTL responses were seen in 2 out of 10 patients. Mannan-MUC1 can immunize patients, particularly for antibody formation, and to a lesser extent, cellular responses. It remains to be seen whether such responses have antitumor activity.
Human Th17 Cells Share Major Trafficking Receptors with Both Polarized Effector T Cells and FOXP3+ Regulatory T Cells (2008)

It is a question of interest whether Th17 cells express trafficking receptors unique to this Th cell lineage and migrate specifically to certain tissue sites. We found several Th17 cell subsets at different developing stages in a human secondary lymphoid organ (tonsils) and adult, but not in neonatal, blood. These Th17 cell subsets include a novel in vivo-stimulated tonsil IL17+ T cell subset detected without any artificial stimulation in vitro. We investigated in depth the trafficking receptor phenotype of the Th17 cell subsets in tonsils and adult blood. The developing Th17 cells in tonsils highly expressed both Th1- (CCR2, CXCR3, CCR5, and CXCR6) and Th2-associated (CCR4) trafficking receptors. Moreover, Th17 cells share major non-lymphoid tissue trafficking receptors, such as CCR4, CCR5, CCR6, CXCR3, and CXCR6, with FOXP3+ T regulatory cells. In addition, many Th17 cells express homeostatic chemokine receptors (CD62L, CCR6, CCR7, CXCR4, and CXCR5) implicated in T cell migration to and within lymphoid tissues. Expression of CCR6 and CCR4 by some Th17 cells is not a feature unique to Th17 cells but shared with FOXP3+ T cells. Interestingly, the IL17+IFN-gamma+ Th17 cells have the features of both IL17-IFN-gamma+ Th1 and IL17+IFN-gamma- Th17 cells in expression of trafficking receptors. Taken together, our results revealed that Th17 cells are highly heterogeneous, in terms of trafficking receptors, and programmed to share major trafficking receptors with other T cell lineages. These findings have important implications in their distribution in the human body in relation to other regulatory T cell subsets.
PREDICTING THE ACUTE INFLAMMATORY RESPONSE IN COMBINED TRAUMA-HEMORRHAGE AND ENDOTOXEMIA USING MATHEMATICAL SIMULATIONS (2004)

Vodovotz, Yoram; Lagoa, Claudio; Day, Judy; Kumar, Rukmini; Chow, Carson; Fink, Mitchell P.; Billiar, Timothy R; Clermont, Gilles Author Information
PARP is important for genomic stability but dispensable in apoptosis (1997)

Mice lacking the gene encoding poly(ADP-ribosyl) transferase (PARP or ADPRT) display no phenotypic abnormalities, although aged mice are susceptible to epidermal hyperplasia and obesity in a mixed genetic background. Whereas embryonic fibroblasts lacking PARP exhibit normal DNA excision repair, they grow more slowly in vitro. Here we investigated the putative roles of PARP in cell proliferation, cell death, radiosensitivity, and DNA recombination, as well as chromosomal stability. We show that the proliferation deficiency in vitro and in vivo is most likely caused by a hypersensitive response to environmental stress. Although PARP is specifically cleaved during apoptosis, cells lacking this molecule apoptosed normally in response to treatment with anti-Fas, tumor neurosis factor alpha, gamma-irradiation, and dexamethasone, indicating that PARP is dispensable in apoptosis and that PARP-/- thymocytes are not hypersensitive to ionizing radiation. Furthermore, the capacity of mutant cells to carry out immunoglobulin class switching and V(D)J recombination is normal. Finally, primary PARP mutant fibroblasts and splenocytes exhibited an elevated frequency of spontaneous sister chromatid exchanges and elevated micronuclei formation after treatment with genotoxic agents, establishing an important role for PARP in the maintenance of genomic integrity.
Effect of the supplemental use of antioxidants vitamin C, vitamin E, and coenzyme Q10 for the prevention and treatment of cancer. (2003)

Patients with cancer commonly try a variety of nontraditional treatments that fit the broad category known as Complementary and Alternative Medicine (CAM).
Nonlinear approximation (1998)

This is a survey of nonlinear approximation, especially that part of the subject which is important in numerical computation. Nonlinear approximation means that the approximants do not come from linear spaces but rather from nonlinear manifolds. The central question to be studied is what, if any, are the advantages of nonlinear approximation over the simpler, more established, linear methods. This question is answered by studying the rate of approximation which is the decrease in error versus the number of parameters in the approximant. The number of parameters usually correlates well with computational effort. It is shown that in many settings the rate of nonlinear approximation can be characterized by certain smoothness conditions which are significantly weaker than required in the linear theory. Emphasis in the survey will be placed on approximation by piecewise polynomials and wavelets as well as their numerical implementation. Results on highly nonlinear methods such as optimal basis selection and greedy algorithms (adaptive pursuit) are also given. Applications to image processing, statistical estimation, regularity for PDEs, and adaptive algorithms are discussed.
Glycan profiles of the 27 N-glycosylation sites of the HIV envelope protein CN54gp140 (2012)

Hope rests on the envelope proteins of human immunodeficiency virus (HIV) as protective vaccines and thus their antibody binding sites are of prime interest. 2G12 and other human antibodies bind to a cluster of oligomannose N-glycans. Owing to the extreme number and density of N-glycosylation sites gp160 and its recombinant form gp140 represent challenging tasks for site-specific glycosylation analysis. We have conducted a glycosylation analysis of CN54gp140 by liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) using an ion trap as well as a Q-TOF instrument and standard software for glycopeptide identification. First, a deglycosylated sample of the protease digest served to locate the elution positions of peptides covering all of the 27 potential N-glycosylation sites. Then, the assignments of the similarly eluting glycopeptides were verified by collision-induced decay MS/MS experiments with elevated fragmentation energy. The acquisition of site-specific glycan profiles was facilitated by the use of buffered eluent, which rounds up all glycoforms of a peptide into one peak. Calculation of the molecular mass drawn on the weighted averages of the glycans at each site led to the actual mass of gp140 of approximately 120 kDa.
Androgen Receptor Modulators: A Marriage of Chemistry and Biology (2013)

Androgenic steroids are important for male development in utero and secondary sexual characteristics at puberty. In addition, androgens play a role in non-reproductive tissues, such as bone and muscle in both sexes. The actions of the androgens testosterone and dihydrotestosterone are mediated by a single receptor protein, the androgen receptor. Over the last 60-70 years there has been considerable research interest in the development of inhibitors of androgen receptor for the management of diseases such as prostate cancer. However, more recently, there is also a growing appreciation of the need for selective androgen modulators that would demonstrate tissue-selective agonist or antagonist activity. The chemistry and biology of selective agonists, antagonists and selective androgen receptor modulators will be discussed in this review.
Semisynthesis of Peptoid–Protein Hybrids by Chemical Ligation at Serine (2014)

Chemical ligation protocols were explored for generating semisynthetic peptoid-protein hybrid architectures containing a native serine residue at the ligation site. Peptoid oligomers bearing C-terminal salicylaldehyde esters were synthesized and ligated to the N-terminus of the RNase S protein or the therapeutic hormone PTH(1-34) polypeptide. This technique will expand the repertoire of strategies to enable design of hybrid macromolecules with novel structures and functions not accessible to fully biosynthesized proteins.
The role of STAT6 in mast cell IL‐4 production (2001)

Interleukin (IL)-4 has an important role in regulating antibody production and inflammation. The major IL-4 producers are CD4+ T cells, but the development of an IL-4-producing phenotype in these cells requires IL-4 signaling through the STAT6 pathway during differentiation. The cellular source of this early IL-4 is not known, but mast cells are a possible candidate due to their immediate and indiscriminate release of IL-4 upon activation. In this review we summarize the evidence that STAT6 signaling is not required for mast cell IL-4 production, which is consistent with their possible role as a link between the innate immune response and T-cell activation. We also describe an isoform of STAT6 that is expressed in mast cells and that appears to act as a repressor of IL-4 transcription. This STAT6 signaling pathway may be part of a feedback mechanism to protect surrounding tissues from IL-4-mediated inflammation during an infection.
Overcoming cisplatin resistance by mTOR inhibitor in lung cancer (2005)

We conclude that CCI-779 is able to restore cisplatin sensitivity in small cell lung cancer cell lines selected for cisplatin resistance as well as cell lines derived from patients who failed cisplatin. These findings can be further explored for future clinical use. On the other hand, CCI-779 at achievable clinical concentration, has no growth inhibitory effect in P-gp1 or MRP1 overexpressing cells. Furthermore, CCI-779 also appears to be a weak MDR1 reversal agent. Thus, it is not a candidate to use in MDR1 or MRP1 overexpressing cells.
Therapy with antibodies against CD40L (CD154) and CD44-variant isoforms reduces experimental autoimmune encephalomyelitis induced by a proteolipid protein peptide (1998)

Interactions between mononuclear cells are required for the formation of inflammatory infiltrates in the CNS and the activation of cellular effector functions provoking demyelination in MS. Membrane-expressed costimulatory molecules are crucial to such interactions. We therefore investigated whether two costimulatory molecules, CD40L (CD154, expressed on activated CD4-possible T cells) and selected CD44-variant isoforms (expressed on activated CD4-positive T cells), are targets for immunotherapy in MS. The model of experimental autoimmune encephalomyelitis (EAE) induced in SJL-mice by immunization with a peptide derived from the proteolipid protein (PLP139-151) was optimized to address these questions. A previous observation that anti-CD40L (CD154) monoclonal antibodies can effectively prevent EAE in this model was confirmed, and extended by demonstrating that CD40 is expressed by cells of the monocytic lineage infiltrating the spinal cord. In vivo treatment with antibody against the standard isoform of CD44 (CD44s or CD44H) did not affect disease burden. In contrast, combined treatment with antibodies against the isoforms CD44v6, v7 and v10, which are thought to be involved in inflammatory processes, reduced the disease burden considerably. In addition, CD44v10-expressing cells were detected in the spinal cord. These data support the idea that CD40-CD40L interactions form a target for immunotherapy of MS, and indicate that cells expressing CD44v6, v7 and/or v10-containing isoforms have such potential as well.
Apparent diffusion coefficient in pancreatic cancer: Characterization and histopathological correlations (2008)

Collagenous fibers may be responsible for diffusion abnormalities in pancreatic cancer.
Innate Allorecognition Results in Rapid Accumulation of Monocyte-Derived Dendritic Cells (2016)

Although the mechanisms governing the innate recognition of pathogen-associated molecular patterns have been well defined, how allogeneic cellular stimuli evoke innate responses remains less so. In this article, we report that upon i.v. transfer (to avoid major iatrogenic interference), allogeneic but not syngeneic leukocytes could induce a rapid (after 1 d) accumulation of host monocyte-derived dendritic cells (moDCs) without any increase in conventional DCs. This occurred in various donor-host strain combinations, did not require MHC mismatch, and could be induced by various donor cell types including B cells, T cells, or NK cells. Using RAG(-/-)γc(-/-) and scid γc(-/-)mice with different MHC, we found that the presence of either donor or host lymphoid cells was required. Alloinduced moDC accumulation was significantly reduced when splenocytes from mice deficient in NK cells by genetic ablation were used as donors. A major component of this moDC accumulation appears to be recruitment. Our findings provide new insights into how the innate and adaptive immune system may interact during allogeneic encounters and thus transplant rejection.
Polarization and Phase Control of Remote Surface-Plasmon-Mediated Two-Photon-Induced Emission and Waveguiding (2006)

We report here on the control of remote surface-plasmon-mediated two-photon-induced luminescence of dendritic silver nanoparticle aggregates as observed by femtosecond laser microscopy. With a focal spot diameter approximately 1 microm, polarized remote emission has been observed 99 microm from the focal spot. We show control over the regions of emission by changing the polarization of the incident beam and by changing the spectral phase of the laser pulse.
Immunotherapy of Malignant Melanoma with Tumor Lysate-Pulsed Autologous Monocyte-Derived Dendritic Cells (2011)

In this study, DC vaccination using tumor antigen-loaded, mature MoDCs led to tumor regression in individual melanoma patients. Further standardization of DC vaccination protocol is required to determine which parameters lead to better anti-tumor responses and clinical outcomes.