gebhart/patrepeval huggingface dataset:
Novel Sequence Determinants in Peroxisome Proliferator Signaling (1995)

The gene encoding cytochrome P-450 4A6 (CYP4A6) is transcriptionally activated by peroxisome proliferators. This response is dependent on a strong enhancer element (Z) and weaker elements (X and -27). The peroxisome proliferator response is mediated by the binding of heterodimers containing the peroxisome proliferator-activated receptor alpha (PPAR alpha) and the retinoid X receptor alpha (RXR alpha) to these elements. These peroxisome proliferator response elements (PPREs) contain imperfect direct repeats of the nuclear receptor consensus recognition sequence with a spacing of one nucleotide (DR1) (AGGTCA N AGGTCA). This DR1 motif is seen in the binding sites for other nuclear receptor complexes, such as ARP-1, HNF-4, and RXR alpha homodimers. Mutational analysis of the Z element reveals that the DR1 motif is required for the transcriptional activation of the CYP4A6 gene by peroxisome proliferators; however, deletion of sequences immediately upstream of this motif also abolishes this response. Oligonucleotides corresponding to truncated and mutated Z elements were assayed by gel retardation for binding to RXR alpha, PPAR alpha, and ARP-1. Deletions or mutations within six nucleotides 5' of the DR1 motif dramatically diminish PPAR alpha.RXR alpha binding without reducing the binding of either RXR alpha or ARP-1 homodimers, whereas mutation or deletion of the core DR1 sequences abolishes the binding of PPAR alpha.RXR alpha heterodimers and of RXR alpha or ARP-1 homodimers. Thus, the DR1 motif in the Z element is not sufficient to constitute a PPRE. Moreover, the binding of PPAR alpha.RXR alpha to the Z element requires sequences immediately 5' of the DR1. These sequences are conserved in natural PPREs and promote binding of PPAR alpha.RXR alpha heterodimers in preference to potential competitors such as ARP-1 and RXR alpha.
Exploring the binding preferences/specificity in the active site of human cathepsin E (1995)

Aspartic proteinases are produced in the human body by a variety of cells. Some of these proteins, examples of which are pepsin, gastricsin, and renin, are secreted and exert their effects in the extracellular spaces. Cathepsin D and cathepsin E on the other hand are intracellular enzymes. The least characterized of the human aspartic proteinases is cathepsin E. Presented here are results of studies designed to characterize the binding specificities in the active site of human cathepsin E with comparison to other mechanistically similar enzymes. A peptide series based on Lys-Pro-Ala-Lys-Phe*Nph-Arg-Leu was generated to elucidate the specificity in the individual binding pockets with systematic substitutions in the P5-P2, and P2'-P3' based on charge, hydrophobicity, and hydrogen bonding. Also, to explore the S2 binding preferences, a second series of peptides based on Lys-Pro-Ile-Glu-Phe*Nph-Arg-Leu was generated with systematic replacements in the P2 position. Kinetic parameters were determined for both sets of peptides. The results were correlated to a rule-based structural model of human cathepsin E, constructed on the known three-dimensional structures of several highly homologous aspartic proteinases; porcine pepsin, bovine chymosin, yeast proteinase A, human cathepsin D, and mouse and human renin. Important specificity-determining interactions were found in the S3 (Glu-13) and S2 (Thr-222, Gln-287, Leu-289, Ile-300) subsites.
On-line learning of parametric mixture models for light transport simulation (2014)

Monte Carlo techniques for light transport simulation rely on importance sampling when constructing light transport paths. Previous work has shown that suitable sampling distributions can be recovered from particles distributed in the scene prior to rendering. We propose to represent the distributions by a parametric mixture model trained in an on-line (i.e. progressive) manner from a potentially infinite stream of particles. This enables recovering good sampling distributions in scenes with complex lighting, where the necessary number of particles may exceed available memory. Using these distributions for sampling scattering directions and light emission significantly improves the performance of state-of-the-art light transport simulation algorithms when dealing with complex lighting.
The HTM Spatial Pooler – a neocortical algorithm for online sparse distributed coding (2016)

1. Abstract Hierarchical temporal memory (HTM) provides a theoretical framework that models several key computational principles of the neocortex. In this paper we analyze an important component of HTM, the HTM spatial pooler (SP). The SP models how neurons learn feedforward connections and form efficient representations of the input. It converts arbitrary binary input patterns into sparse distributed representations (SDRs) using a combination of competitive Hebbian learning rules and homeostatic excitability control. We describe a number of key properties of the spatial pooler, including fast adaptation to changing input statistics, improved noise robustness through learning, efficient use of cells and robustness to cell death. In order to quantify these properties we develop a set of metrics that can be directly computed from the spatial pooler outputs. We show how the properties are met using these metrics and targeted artificial simulations. We then demonstrate the value of the spatial pooler in a complete end-to-end real-world HTM system. We discuss the relationship with neuroscience and previous studies of sparse coding. The HTM spatial pooler represents a neurally inspired algorithm for learning sparse representations from noisy data streams in an online fashion.
Crystal Structure of a Mucus-binding Protein Repeat Reveals an Unexpected Functional Immunoglobulin Binding Activity (2009)

Lactobacillus reuteri mucus-binding protein (MUB) is a cell-surface protein that is involved in bacterial interaction with mucus and colonization of the digestive tract. The 353-kDa mature protein is representative of a broadly important class of adhesins that have remained relatively poorly characterized due to their large size and highly modular nature. MUB contains two different types of repeats (Mub1 and Mub2) present in six and eight copies, respectively, and shown to be responsible for the adherence to intestinal mucus. Here we report the 1.8-A resolution crystal structure of a type 2 Mub repeat (184 amino acids) comprising two structurally related domains resembling the functional repeat found in a family of immunoglobulin (Ig)-binding proteins. The N-terminal domain bears striking structural similarity to the repeat unit of Protein L (PpL) from Peptostreptococcus magnus, suggesting binding in a non-immune Fab-dependent manner. A distorted PpL-like fold is also seen in the C-terminal domain. As with PpL, Mub repeats were able to interact in vitro with a large repertoire of mammalian Igs, including secretory IgA. This hitherto undetected activity is consistent with the current model that antibody responses against commensal flora are of broad specificity and low affinity.
Corrector-mediated rescue of misprocessed CFTR mutants can be reduced by the P-glycoprotein drug pump (2011)

The most common cause of cystic fibrosis is deletion of Phe508 in the first nucleotide-binding domain (NBD) of the CFTR chloride channel, which inhibits protein folding. ΔF508 CFTR can be rescued by indirect approaches such as low temperature but the protein is unstable. Here, we tested our predictions that (1) other CFTR mutants such V232D and H1085R were more stable at the cell surface than ΔF508 CFTR after low temperature rescue and (2) the advantages of rescue with specific correctors (pharmacological chaperones) are that they may stabilize ΔF508 CFTR and increase the effectiveness of the correctors by bypassing drug pumps such as P-glycoprotein (P-gp) (increased bioavailability). It was found that the stability of mutants V232D and H1085R after low-temperature (30°C) rescue was about 10-fold higher than ΔF508 CFTR. We show that the corrector, 4,5,7-trimethyl-N-phenylquinolin-2-amine (5a), could stabilize ΔF508 CFTR at the cell surface. Unlike most correctors, corrector 5a showed specificity for CFTR as it did not rescue the G268V P-gp processing mutant nor stimulate the ATPase activity of wild-type P-gp. By contrast, corrector KM11060 was a P-gp substrate as it stimulated P-gp ATPase activity and rescued the G268V mutant. Expression of wild-type P-gp reduced the effectiveness of CFTR rescue by corrector KM11060 by about 5-fold. The results underlie the importance of selecting correctors that are specific for CFTR because their efficiency can be reduced by drug pumps such as P-gp.
Alterations in Hepatic FGF21, Co-Regulated Genes, and Upstream Metabolic Genes in Response to Nutrition, Ketosis and Inflammation in Peripartal Holstein Cows (2015)

In rodents, fibroblast growth factor 21 (FGF21) has emerged as a key metabolic regulator produced by liver. To gather preliminary data on the potential importance of FGF1, co-regulated genes, and upstream metabolic genes, we examined the hepatic mRNA expression in response to nutrition and inflammation in dairy cows. In experiment 1, induction of ketosis through feed restriction on d 5 postpartum upregulated FGF21, its co-receptor KLB, and PPARA but only elicited a numerical increase in serum FGF21 concentration. In experiment 2, cows in control (CON) or receiving 50 g/d of L-carnitine (C50) from -14 through 21 d had increased FGF21, PPARA, and NFIL3 on d 10 compared with d 2 postpartum. In contrast, compared with CON and C50, 100 g/d L-carnitine (C100) resulted in lower FGF21, KLB, ANGPTL4, and ARNTL expression on d 10. In experiment 3, cows were fed during the dry period either a higher-energy (OVE; 1.62 Mcal/kg DM) or lower-energy (CON; 1.34 Mcal/kg DM) diet and received 0 (OVE:N, CON:N) or 200 μg of LPS (OVE:Y, CON:Y) into the mammary gland at d 7 postpartum. For FGF21 mRNA expression in CON, the LPS challenge (CON:Y) prevented a decrease in expression between d 7 and 14 postpartum such that cows in CON:N had a 4-fold lower expression on d 14 compared with d 7. The inflammatory stimulus induced by LPS in CON:Y resulted in upregulation of PPARA on d 14 to a similar level as cows in OVE:N. In OVE:Y, expression of PPARA was lower than CON:N on d 7 and remained unchanged on d 14. On d 7, LPS led to a 4-fold greater serum FGF21 only in OVE but not in CON cows. In fact, OVE:Y reached the same serum FGF21 concentration as CON:N, suggesting a carryover effect of dietary energy level on signaling mechanisms within liver. Overall, results indicate that nutrition, ketosis, and inflammation during the peripartal period can alter hepatic FGF21, co-regulated genes, and upstream metabolic genes to various extents. The functional outcome of these changes merits further study, and in particular the mechanisms regulating transcription in response to changes in energy balance and feed intake.
New RNA polymerase sigma factor under spo0 control in Bacillus subtilis. (1986)

In Bacillus subtilis transcription of spoVG is activated within minutes after the initiation of sporulation. Mutations in several spo0 genes prevent the activation of spoVG transcription. We have found a sigma-like protein that is capable of directing core RNA polymerase to use the spoVG promoter in an in vitro run-off transcription assay. This sigma-like protein was not found to be associated with RNA polymerase in a spo0A or spo0B mutant but was present in a spo0H mutant. We suggest that one role of the spo0A gene product in transcription of spoVG is the modulation of RNA polymerase activity by this sigma-like protein.
Photon-Induced Micro/Nano Fabrication, Manipulation, and Imaging with Unconventional Photo-Active Systems (1998)

Abstract We describe about the optical technologies of fabrication, control and imaging of micro/nano structures using unconventional photo-active systems. A focused beam of a near-infrared pulsed laser with a peak power of some ten kilowatts scans in three dimensions to form three- dimensional micro-structures such as micro-tubes and micro-coils with photo-polymerizable material, based on two-photon excitation/absorption process. Three-dimensional optical data-storage which contains data in a volumetric medium is also realized with two-photon process in a photorefractive crystal or with a photochromic molecule for recording and with confocal microscopic optics for phase-reading. We will also show our experimental result of self-growing of micro-fiber in photopolymer by the exposure of a stationary focused laser beam. These technologies can be coupled with the currently progressing near-filed optical technology for observation, fabrication and control of nanometric structures.
Adjustable Silicone Gastric Banding Adverse Events Reported to the Food and Drug Administration (2003)

A silicone adjustable gastric banding system was approved by the Food and Drug Administration (FDA) in June, 2001. The purpose of this report is to review and characterize the reports on silicone adjustable gastric banding systems received by the FDA through August 8, 2002. We also review medical literature on adverse events with silicone adjustable gastric banding systems. Manufacturers of regulated medical devices, such as adjustable silicone gastric bands, are required to report adverse events, including deaths and serious injuries, to the FDA. We reviewed all such reports received by the FDA through August 8, 2002, for adjustable silicone gastric bands and summarize the data by type of adverse event, reported device problems, and reported patient problems. The FDA received 556 reports of adverse events related to the use of adjustable silicone gastric bands. Two of these reports were for deaths, one during surgery and the other as a result of an erosion of the gastric band into the stomach 9 weeks after implantation. Forty-four reports were for injuries including band erosions, slippage, and infection. The most common type of report (499) was for device malfunction, and of these, 485 (97.2%) described a leak at or near the port. Of the 485 leaks reported as malfunctions, 99.4% were treated surgically. The majority of reports were related to disconnection, breakage, and leakage at or near the access port. Physicians and potential patients should be aware of these problems and recognize the possibility that additional surgery(ies) may be required for leaking access port/connections. The loose connection may cause pain and the device no longer performs as intended when there is a leak.
Effective Induction of Acquired Resistance toListeria monocytogenesby Immunizing Mice with In Vivo-Infected Dendritic Cells (2002)

Splenic dendritic cells (DCs) obtained from mice at 48 h after Listeria monocytogenes infection exhibited up-regulation of CD80 and produced higher titers of gamma interferon (IFN-gamma) and interleukin-12 (IL-12) than did DCs obtained from uninfected mice. Mice immunized with DCs obtained from mice that had been infected with L. monocytogenes 48 h before acquired host resistance to lethal infection with L. monocytogenes at 4 and 8 weeks. Immunization with DCs from heat-killed L. monocytogenes failed to induce resistance. Acquired antilisterial resistance is specific, since the immunized mice could not be protected from Salmonella enterica serovar Typhimurium infection. Infected DCs stimulated proliferation of naive CD4(+) and CD8(+) cells in vitro, suggesting that in vivo-infected DCs activate CD8(+) T cells, which are critical in acquired antilisterial resistance, as well as CD4(+) T cells. When wild-type mice were immunized with DCs from IFN-gamma-deficient mice, they were protected against a lethal L. monocytogenes challenge. In contrast, when mice were immunized with DCs from anti-IL-12 p40 monoclonal antibody-injected mice, they failed to gain acquired antilisterial resistance. These results suggest that DC-derived IL-12, but not IFN-gamma, may play a critical role in induction of acquired antilisterial resistance. Our present results suggest that splenic DCs obtained from mice infected with L. monocytogenes in vivo may be an effective immunogen with which to induce antigen-specific immunity.
Surface-Enhanced Raman Detection of Nerve Agent Simulant (DMMP and DIMP) Vapor on Electrochemically Prepared Silver Oxide Substrates (1996)

Surface-enhanced Raman scattering (SERS) spectra of the chemical nerve agent simulants dimethyl methylphosphonate (DMMP) and diisopropyl methylphosphonate (DIMP) were obtained in the vapor phase. The spectra obtained demonstrate the possibility of detecting these nerve agent species in the vapor phase using electrochemically roughened silver oxide substrates prepared from silver foil.
Generating Data for Databases—The Peptide Repertoire of HLA Molecules (2003)

During the past few years, a huge amount of information about HLA-presented peptides has been compiled: several thousand naturally processed ligands of such cell surface receptors are already known. Nevertheless, our knowledge covers only a minute proportion of the total peptide repertoire. The overall amount of different peptides presented by one given HLA class I molecule lies between 1000 and 10000 individual sequences per cell. There is, however, no HLA molecule of which more than 100 ligands have been published so far. The situation is further complicated by the fact that different cells present different sets of peptides by the same HLA molecules, a feature that provides great hope for immunotherapy. We have been analysing HLA-presented peptides for many years for three reasons. First, the basic rules of peptide presentation (the 'peptide motifs') had to be established. Second, the listing of individual peptides presented by HLA molecules is steadily continuing, although a comprehensive catalogue of all possible HLA-presented peptides is utopical in our days. Third, quantitative differences in the presentation of individual HLA ligands provide information about the dynamic state of the host cells. Comprehensive information about HLA-presented peptides enables accurate epitope prediction and provides a basis for diagnostic assessment and therapeutic intervention.
Gene Transfer in Human Lymphocytes Using a Vector Based on Adeno-Associated Virus (1992)

Adeno-associated virus is a nonpathogenic, dependent parvovirus that integrates at a specific site in human chromosome 19. We have used the inverted terminal repeats of the virus, which mediate integration, to establish a vector for gene transfer in human lymphocytes. A neomycin resistance gene has been stably introduced into nontransformed human T-cell clones and a subsequent analysis of the functional properties of the infected clone revealed no detectable alterations. Rescue and replication of the wild-type virus was accomplished with adenovirus superinfection; however, the vector was not rescued and did not replicate by this procedure, indicating the stability of the integrated vector and demonstrating an additional level of safety incorporated in its construction. An adeno-associated virus-based vector represents an alternative to retroviruses for gene therapy in lymphocytes.
Contractile effect of the chemotactic factors f-Met-Leu-Phe and C5a on the human isolated umbilical artery. Role of cyclooxygenase products and tissue macrophages. (1990)

Factors that are chemotactic for phagocytic leukocytes are known to elicit important acute circulatory changes, and the role of circulating leukocytes in these models is controversial. To evaluate the role of the blood vessel wall in the absence of circulating cells, spiral strips of human umbilical artery were exposed in vitro to the chemotactic peptides f-Met-Leu-Phe (1-100 nM) or C5a (2.5-25 nM). Contractile responses were observed for both peptides. Certain agonist analogues and a selective antagonist of the chemotactic action of f-Met-Leu-Phe behaved correspondingly as agonists and antagonist of the contractile effect on umbilical artery. The anaphylatoxin C3a also exerted a contractile effect on the tissue (25 nM and above), but this effect was highly tachyphylactic. Inhibitory drugs were used to examine the contributions of secondary mediators in eliciting the effects of C5a and f-Met-Leu-Phe. The contractile effect of both peptides was massively inhibited either by indomethacin or the thromboxane A2/prostaglandin H2 antagonist SQ 29548. Dazmegrel, a thromboxane A2 synthetase inhibitor, had partial inhibitory effects on contractions induced by either peptide. The contractile effect of C3a was prevented by indomethacin pretreatment. Vascular strips did not release measurable histamine in the bathing fluid after challenge with C5a or f-Met-Leu-Phe. The tissue apparently contains neither histamine nor mast cells. Autoradiography of 125I-labeled C5a or f-Met-Leu-Phe analogue showed specific binding of the peptides to cells dispersed in the vessel wall, but more frequently at the periphery. Cells stained positively for alpha-naphthyl acetate esterase showed a similar distribution. Pure cultures of smooth muscle cells derived from the umbilical artery failed to release prostanoids when exposed to f-Met-Leu-Phe or C5a, whereas fresh strips of this artery released more thromboxane B2 than the baseline in response to these peptides. We conclude that macrophagelike cells, present in the vessel wall, are the likely target cells for the chemotactic peptides. These cells trigger a contractile effect of the smooth muscle by generating cyclooxygenase products.
CD36 participates in the phagocytosis of rod outer segments by retinal pigment epithelium (1996)

Mechanisms of phagocytosis are complex and incompletely understood. The retinal pigment epithelium provides an ideal system to study the specific aspects of phagocytosis since an important function of this cell is the ingestion of packets of membranous discs that are normally discarded at the apical ends of rod and cone cells during outer segment renewal. Here we provide evidence that rod outer segment phagocytosis by retinal pigment epithelium is mediated by CD36, a transmembrane glycoprotein which has been previously characterized on hematopoietic cells as a receptor for apoptotic neutrophils and oxidized low density lipoprotein. Immunocytochemical staining with monoclonal and polyclonal antibodies demonstrated CD36 expression by both human and rat retinal pigment epithelium in transverse cryostat sections of normal retina and in primary cultured cells. By western blot analysis of retinal pigment epithelial cell lysates, polyclonal and monoclonal antibodies to CD36 recognized an 88 kDa protein which comigrated with platelet CD36. Furthermore, the synthesis of CD36 mRNA by retinal pigment epithelium was confirmed by reverse transcriptase-PCR using specific CD36 oligonucleotides. The addition of CD36 antibodies to cultured retinal pigment epithelial cells reduced the binding and internalization of 125I-labeled rod outer segments by 60%. Immunofluorescence confocal microscopy confirmed that outer segment uptake was significantly diminished by an antibody to CD36. Moreover, we found that transfection of a human melanoma cell line with CD36 cDNA enabled these cells to bind and internalize isolated photoreceptor outer segments as seen by double immunofluorescent staining for surface bound and total cell-associated rod outer segments, and by measurement of cell-associated 125I-labeled rod outer segments. We conclude that the multifunctional scavenger receptor CD36 participates in the clearance of photoreceptor outer segments by retinal pigment epithelium and thus, participates in the visual process.