gebhart/patrepeval huggingface dataset:
Viral Internal Ribosome Entry Site Elements: Novel Ribosome-RNA Complexes and Roles in Viral Pathogenesis (2003)

Viruses have multifaceted approaches to ensure that viral genome amplification can be achieved in an efficient and, in some instances, a cell-type-specific manner. To accomplish this task, some viruses encode their own polymerases which selectively amplify the viral genomes; other viruses have evolved a variety of ways to compete directly with the host cell for factors that are needed for viral gene replication and packaging (5). However, there is one piece of macromolecular machinery in the host cell for which all viruses have to compete: the ribosome. Early in infection, the viral mRNAs have to compete with the host, not so much for ribosomes, but for the limited pool of eukaryotic initiation factors (eIFs) that mediate the recruitment of ribosomes to both viral and cellular mRNAs (10). To circumvent this competition, viruses often modify certain eIFs within infected cells so that ribosomes can be recruited selectively to viral mRNAs even though only a limited repertoire of eIFs is present (2). Of course, this strategy implies that such viral mRNAs have structural features that are distinct from most polymerase II-derived host mRNAs.

For example, it was a long-standing puzzle how poliovirus, a human picornavirus, can inhibit the translation of capped host cell mRNAs when translation of its own uncapped mRNA remained uninhibited. More than a decade ago, it was discovered that poliovirus, and all other picornaviruses, contain internal ribosome entry site elements, commonly abbreviated as IRES elements, in their 5′ noncoding regions that can directly recruit ribosomal 40S subunits with a reduced set of eIFs (13, 24). The cap binding protein eIF-4E is especially dispensable for IRES activity in most viral IRES-containing mRNAs. Since then, IRES elements have been detected in many positive-stranded viral RNA genomes (9). More recently, IRESs have also been identified in Kaposi's sarcoma-associated herpesvirus, which contains a DNA genome. Specifically, a polycistronic transcript, found in all latently infected cells, is used to express the v-FLIP (FLICE-inhibitory protein) protein whose function is to counteract fatty acid synthase-induced apoptosis (1, 7). These findings have provided ample evidence that IRES elements have important functions in the viral life cycle, mostly to ensure efficient viral translation when components of the host translation machinery are limited due to virus-induced modification or host-induced antiviral responses, such as the phosphorylation of eIF-2 (9).

In this minireview, I will discuss the surprising structural information we have obtained from studies on binary hepatitis C virus (HCV) IRES-40S complexes and the roles of specific canonical initiation and IRES-transacting factors (ITAFs) in translation initiation and in viral pathogenesis. I apologize for not mentioning and citing the many important contributions of other investigators who have made contributions in the viral IRES field. Due to space constraints in this minireview, I needed to focus on a few selected topics.
VSV-G Envelope Glycoprotein Forms Complexes with Plasmid DNA and MLV Retrovirus-like Particles in Cell-free Conditions and Enhances DNA Transfection (2001)

We have previously shown that vesicles containing the spike glycoprotein of the vesicular stomatitis virus (VSV-G) can associate efficiently with immature, non-infectious, envelope-deficient retrovirus-like particles assembled by packaging cells to produce infectious, pseudotyped viruses in cell-free conditions in vitro. We have also previously reported that VSV-G can enhance DNA lipofection efficiency by interacting with liposomes to form fusogenic, serum-stable liposomes with enhanced transfection properties. Here, we report that VSV-G can form a complex directly with naked plasmid DNA in the absence of a lipofection reagent and can thereby enhance the transfection efficiency of the naked plasmid vector. Sucrose gradient sedimentation analysis demonstrated that VSV-G can also associate with plasmid DNA and murine leukemia virus (MLV) gag-pol particles to form ternary complexes that co-sediment with high DNA transfecting activity. The increased transfection efficiency with VSV-G was dependent on the presence of the polycation (Polybrene) in the culture medium during transfection. Enhanced transfection was abolished by a neutralizing antibody to VSV-G. These results may be useful in the study of retrovirus assembly, in the further design of hybrid DNA-based retrovirus-like vectors, and in the full in vitro, cell-free assembly of infectious virus-like particles from component parts.
Collision detection of manipulator based on adaptive control law (2002)

In this paper, we propose a collision detection method of a manipulator based on the nonlinear adaptive control law proposed by Slotine and Li (1988). The collision of a manipulator with its environment is detected by the difference between the actual input torques to the manipulator and the reference input torques calculated based on the manipulator dynamics. An adaptive control scheme is employed for the manipulator control and the parameter estimation of the manipulator. The reference input torques are calculated using the estimated manipulator parameters. The proposed collision detection scheme is applied to an industrial manipulator and the experimental results illustrate the validity of the proposed scheme.
Activation of antigen-enriched B cells. II. Role of linked recognition in B cell proliferation to thymus-dependent antigens. (1983)

The responsiveness to T-dependent (TD) and T-independent (TI) TNP-antigens of murine splenic B cells previously enriched for antigen-binding cells (ABC) was examined. TNP-TI antigens induced B cell proliferation. TNP-TD antigens did not induce a proliferative response regardless of the physical form or nature of the TNP-TD antigen (e.g., soluble vs particulate, low or high haptenation of carrier, TNP on various insoluble matrices, etc.). TNP-TD antigens were effective in enhancing the response of the TNP-ABC to all concentrations of lipopolysaccharide (LPS) tested, indicating that binding of antigen to surface immunoglobulin alters the LPS responsiveness of the cell. Irradiated, keyhole limpet hemocyanin- (KLH) primed T cells induced a threefold to fourfold greater B cell proliferative response with TNP-KLH than with fluoresceinated KLH (FLU-KLH) or FLU-KLH together with TNP-human serum albumin (TNP-HSA). Therefore, linked recognition appears essential for optimal T cell-mediated B cell proliferation, whereas the induction of B cell proliferation via nonlinked, carrier-activated T cells is a minor component of the response.
Nanostructure‐Driven Analyte–Interface Electron Transduction: A General Approach to Sensor and Microreactor Design (2011)

A concept describing the nanostructure-directed dynamics of acid/base interaction and the balance between physisorption and chemisorption on an extrinsic semiconductor interface is evaluated and compared for n- and p-type semiconductors. The inverse hard/soft acid/base (IHSAB) concept, as it complements the HSAB concept, defines the nature of a dominant physisorption behavior and enables the creation of a matrix of controllable interactions. The technology results in the coupling of Lewis acid/base chemistry with the extrinsic semiconductor majority carriers. Nanoporous silicon layers facilitate the application of nanostructured metal/metal oxides, which provide sensitivity and selectivity for the modified interface. Applied fractional depositions can produce a dominant reversible physisorptive (sensors) or chemisorptive (microreactors) interaction at the semiconductor interface as the nanostructures act as antennas to focus the interaction. The dynamic natures of n- and p-type silicon are evaluated and compared, by focusing on the controlled manipulation of these semiconductors as they are modified with nanostructures and interact with the gas-phase analytes. The observed semiconductor responses correlate well with the temperature dependence of the extrinsic semiconductor, the population of the donor or acceptor levels, and the inherent mobilities of electrons. The response of the modified n-type semiconductors is found to exceed that of comparable p-type systems. The IHSAB concept can be extended to assess the properties of several additional semiconductor interfaces including nanowires. The results obtained not only pertain to sensor and microreactor array design, but also suggest the importance of the dynamic changes created, as the majority charge-carrier concentrations are manipulated and the Fermi energies are modified through chemical interaction.
Mucopolysaccharidosis type I: identification of 8 novel mutations and determination of the frequency of the two common α-L-iduronidase mutations (W402X and Q70X) among European patients (1994)

A group of 46 European patients with mucopolysaccharidosis type I (MPS I) was screened for mutations of the alpha-L-iduronidase gene. The 2 common nonsense mutations, W402X and Q70X, were identified in, respectively, 37% and 35% of mutant alleles. Considerable differences were seen in the frequency of these 2 mutations in patients from North Europe (Norway and Finland) and other European countries (mainly The Netherlands and Germany). In Scandinavia, W402X and Q70X account for 17% and 62% of the MPS I alleles, respectively, while in other European countries W402X is about 2.5 times more frequent (48%) than Q70X (19%). Eight novel mutations are described including 4 missense mutations, 1 nonsense mutation, 1 insertion of 2 base pairs, and 2 deletions of 1 and 12 base pairs.
Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases (2003)

Matrix metalloproteinases (MMPs), also designated matrixins, hydrolyze components of the extracellular matrix. These proteinases play a central role in many biological processes, such as embryogenesis, normal tissue remodeling, wound healing, and angiogenesis, and in diseases such as atheroma, arthritis, cancer, and tissue ulceration. Currently 23 MMP genes have been identified in humans, and most are multidomain proteins. This review describes the members of the matrixin family and discusses substrate specificity, domain structure and function, the activation of proMMPs, the regulation of matrixin activity by tissue inhibitors of metalloproteinases, and their pathophysiological implication.
Biodistribution of AAV8 Vectors Expressing Human Low-Density Lipoprotein Receptor in a Mouse Model of Homozygous Familial Hypercholesterolemia (2013)

Recombinant adeno-associated viral vectors based on serotype 8 (AAV8) transduce liver with superior tropism following intravenous (IV) administration. Previous studies conducted by our lab demonstrated that AAV8-mediated transfer of the human low-density lipoprotein receptor (LDLR) gene driven by a strong liver-specific promoter (thyroxin-binding globulin [TBG]) leads to high level and persistent gene expression in the liver. The approach proved efficacious in reducing plasma cholesterol levels and resulted in the regression of atherosclerotic lesions in a murine model of homozygous familial hypercholesterolemia (hoFH). Prior to advancing this vector, called AAV8.TBG.hLDLR, to the clinic, we set out to investigate vector biodistribution in an hoFH mouse model following IV vector administration to assess the safety profile of this investigational agent. Although AAV genomes were present in all organs at all time points tested (up to 180 days), vector genomes were sequestered mainly in the liver, which contained levels of vector 3 logs higher than that found in other organs. In both sexes, the level of AAV genomes gradually declined and appeared to stabilize 90 days post vector administration in most organs although vector genomes remained high in liver. Vector loads in the circulating blood were high and close to those in liver at the early time point (day 3) but rapidly decreased to a level close to the limit of quantification of the assay. The results of this vector biodistribution study further support a proposed clinical trial to evaluate AAV8 gene therapy for hoFH patients.
Reovirus-induced acute myocarditis in mice correlates with viral RNA synthesis rather than generation of infectious virus in cardiac myocytes (1996)

The capacity for different reovirus reassortant viruses to induce acute myocarditis in mice correlates with cytopathogenic effect in primary cultures of murine cardiac myocytes. Multiple viral genes encoding proteins involved in viral RNA synthesis are determinants of this disease. We therefore evaluated the role of viral RNA synthesis in induction of acute myocarditis by infecting primary cultures of cardiac myocytes with a panel of myocarditic and nonmyocarditic viruses and quantitating RNA synthesis. RNA synthesis correlated with induction of myocarditis and with the S1 and M1 reovirus genes. Since one consequence of viral RNA synthesis is generation of infectious virus, we looked next at viral yield from cardiac myocyte cultures. Yield of infectious virus at an early time postinfection or as a final yield from primary infections did not correlate with myocarditis, but instead both correlated with the S1 gene. The S1 gene also determined the fraction of cells infected during primary infections in the culture, which varied dramatically between viruses. Viral yields per infected cell were similar for most myocarditic and nonmyocarditic reoviruses and did not correlate with induction of myocarditis or any reovirus gene. Together, the data provide two insights into reovirus-induced acute myocarditis in mice. First, while the S1 gene. which encodes the viral attachment protein sigma1 (as well as a nonstructural protein, sigma1s, of unknown function) does not determine the myocarditic potential of these viruses, it does determine the efficiency with which they infect cardiac myocytes. Second, while viral RNA synthesis is a determinant of acute myocarditis, this is not due to generation of infectious virus. This finding suggests that some other consequence of viral RNA synthesis, for example, induction of interferon, may determine reovirus-induced acute myocarditis.
Perchlorate degradation using partially oxidized titanium ions and ion exchange membrane hybrid system (2010)

Perchlorate has entered human and environmental food chains and has received a great deal of attention because of its toxicity to humans. In this study, chemical degradation of perchlorate was investigated using partially oxidized titanium ions (Ti2+ and Ti3+) in solutions and as part of an ion exchange membrane reactor system. Aqueous titanium ions (Ti2+ and Ti3+) were applied to remove perchlorate ions and its destructive mechanism, reaction kinetics, and the effect of environmental factors were investigated. Titanium ions were able to degrade perchlorate ions very rapidly with half life less than one hour under conditions of high acid concentrations. A new reactor system with an ion exchange membrane was adapted to apply better the reactions of perchlorate destruction to water treatment practice. A novel treatment method was developed by integrating partially oxidized titanium ions with an ion exchange membrane, and it is named the Titanium and Membrane Hybrid System (TMH System). The results shown in this research demonstrate the feasibility of TMH System for perchlorate reduction. The perchlorate ions were rapidly adsorbed onto the ion exchange membrane and diffused through it, but they were reduced by titanium ions in the degradation zone relatively slowly. To enhance the overall rate of reaction, high concentrations of acid and Ti(III) are needed, but transport of hydrogen ions through the anion permeable membrane was observed and would be greater at higher acid concentrations. The proposed mathematical model predicts the performance and behavior of the TMH system for different physical and chemical conditions. It successfully described adsorption, diffusion and reduction of perchlorate in the system. This model could be used as an important tool for process design and optimization.
Homology modeling, model and software evaluation: three related resources. (1998)

gert.vriend@embl-heidelberg.de
New Lessons for Combinatorial Biosynthesis from Myxobacteria (1999)

The biosynthetic mta gene cluster responsible for myxothiazol formation from the fruiting body forming myxobacterium Stigmatella aurantiaca DW4/3-1 was sequenced and analyzed. Myxothiazol, an inhibitor of the electron transport via the bc(1)-complex of the respiratory chain, is biosynthesized by a unique combination of several polyketide synthases (PKS) and nonribosomal peptide synthetases (NRPS), which are activated by the 4'-phosphopantetheinyl transferase MtaA. Genomic replacement of a fragment of mtaB and insertion of a kanamycin resistance gene into mtaA both impaired myxothiazol synthesis. Genes mtaC and mtaD encode the enzymes for bis-thiazol(ine) formation and chain extension on one pure NRPS (MtaC) and on a unique combination of PKS and NRPS (MtaD). The genes mtaE and mtaF encode PKSs including peptide fragments with homology to methyltransferases. These methyltransferase modules are assumed to be necessary for the formation of the proposed methoxy- and beta-methoxy-acrylate intermediates of myxothiazol biosynthesis. The last gene of the cluster, mtaG, again resembles a NRPS and provides insight into the mechanism of the formation of the terminal amide of myxothiazol. The carbon backbone of an amino acid added to the myxothiazol-acid is assumed to be removed via an unprecedented module with homology to monooxygenases within MtaG.
Screens Using RNAi and cDNA Expression as Surrogates for Genetics in Mammalian Tissue Culture Cells (2005)

We have developed methods for the automation of transfection-grade DNA preparation, high-throughput retroviral preparation, and highly parallel phenotypic screens to establish approaches that will allow investigators to examine in an unbiased manner the roles of proteins in mammalian cells. These methods have been used to raise or lower the levels of individual kinases in individual micro-well cultures either by cDNA or short hairpin RNA expression and will allow investigators to treat mammalian cells in culture in manners that are analogous to genetic screens in yeast. Our proof-of-principle experiments have been performed in human cells using repositories that represent over 75% of the protein, nucleotide, carbohydrate, lipid, and amino acid kinases in the human genome. These initial experiments have demonstrated the feasibility of two general types of screens. We have performed phenotypic screens to identify proteins with specific roles in a chosen function and genetic interaction screens to establish epistatic relations between different proteins. The results suggest that any phenotype that can be scored by a robust assay in tissue culture is amenable to these types of screens and that interactions between mammalian proteins can be established. These results point to the near-term goal of establishing comprehensive, unbiased screens that will allow queries on the roles of all human proteins.
Maintenance of Peripheral Tolerance through Controlled Tissue Homing of Antigen-Specific T Cells in K14-mOVA Mice (2009)

Immunological tolerance is crucial to avoid autoimmune and inflammatory diseases; however, the mechanisms involved are incompletely understood. To study peripheral tolerance to skin-associated Ags, we generated new transgenic mice expressing a membrane-bound form of OVA in skin under the human keratin 14 (K14) promoter (K14-mOVA mice). In contrast to other transgenic mice expressing similar self-Ags in skin, adoptive transfer of Ag-specific T cells does not induce inflammatory skin disease in our K14-mOVA mice. OVA-specific T cells transferred into K14-mOVA mice are activated in lymphoid tissues, undergo clonal expansion, and eventually acquire effector function. Importantly, these Ag-specific T cells selectively up-regulate expression of E-selectin ligand in cutaneous lymph nodes but not in mesenteric lymph nodes and spleen, demonstrating that expression of endogenous self-Ags in skin dictates imprinting of skin tissue homing in vivo. However, an additional inflammatory signal, here induced by tape stripping, is required in K14-mOVA mice to induce T cell migration to skin and development of inflammatory skin disease. Depletion of regulatory CD4(+)CD25(+) T cells did not provoke homing of transferred T cells to skin under steady-state conditions, indicating that these cells are not the key regulators for inhibiting T cell homing in K14-mOVA mice. Both skin-derived and lymph node-resident CD8alpha(+) dendritic cells are responsible for Ag presentation in vivo and induce tolerance to skin Ags, as we show by selective depletion of langerin(+) and CD11c(+) dendritic cells. Taken together, controlled skin homing of T cells is critical for the maintenance of peripheral immune tolerance to epidermal self-Ags.
Retroviral vector infection and transplantation in rats of primary fetal rat hepatocytes (1991)

Retroviral vectors were used to transduce recombinant DNA encoding firefly luciferase, Escherichia coli beta-galactosidase or human factor IX into fetal rat hepatocytes in primary culture. Hepatocytes were transduced optimally during a restricted time interval, 2-4 days post-plating. Although efficient and stable expression of reporter gene products was observed in vitro, it was affected differentially by culture conditions (plating density, media constituents) and chemical modulators of hepatocyte growth and differentiation (gelatin, hydrocortisone, isobutylmethylxanthine). Cultured cells, mock-infected or infected with a luciferase-expressing vector, were harvested non-enzymatically and injected subcutaneously into the dorsal neck fascia of neonatal syngeneic rats. Tissue isolated from injection sites one week later contained hepatocyte foci. In animals transplanted with infected cells, the preliminary results suggest that luciferase activity was present at these sites in proportion to the numbers of injected cells. These findings and previous observations made with hepatocytes from neonatal and adult primary cultures, indicate that from day 19 in utero through maturity the transient temporal 'period of susceptibility' to infection in vitro is independent of the developmental state of starting tissue. Transplantability of cultured fetal hepatocytes infected with retroviral vectors and stably expressing reporter gene products suggests that such cells might provide promising models for liver gene therapy.
Kinetic Analysis of Multiple Proton Shuttles in the Active Site of Human Carbonic Anhydrase (2002)

We have prepared a site-specific mutant of human carbonic anhydrase (HCA) II with histidine residues at positions 7 and 64 in the active site cavity. Using a different isozyme, we have placed histidine residues in HCA III at positions 64 and 67 and in another mutant at positions 64 and 7. Each of these histidine residues can act as a proton transfer group in catalysis when it is the only nonliganding histidine in the active site cavity, except His(7) in HCA III. Using an (18)O exchange method to measure rate constants for intramolecular proton transfer, we have found that inserting two histidine residues into the active site cavity of either isozyme II or III of carbonic anhydrase results in rates of proton transfer to the zinc-bound hydroxide that are antagonistic or suppressive with respect to the corresponding single mutants. The crystal structure of Y7H HCA II, which contains both His(7) and His(64) within the active site cavity, shows the conformation of the side chain of His(64) moved from its position in the wild type and hydrogen-bonded through an intervening water molecule with the side chain of His(7). This suggests a cause of decreased proton transfer in catalysis.