gebhart/patrepeval huggingface dataset:
Conversion of Tyrosine Phenol-lyase to Dicarboxylic Amino Acid β-Lyase, an Enzyme Not Found in Nature (1999)

Tyrosine phenol-lyase (TPL), which catalyzes the beta-elimination reaction of L-tyrosine, and aspartate aminotransferase (AspAT), which catalyzes the reversible transfer of an amino group from dicarboxylic amino acids to oxo acids, both belong to the alpha-family of vitamin B6-dependent enzymes. To switch the substrate specificity of TPL from L-tyrosine to dicarboxylic amino acids, two amino acid residues of AspAT, thought to be important for the recognition of dicarboxylic substrates, were grafted into the active site of TPL. Homology modeling and molecular dynamics identified Val-283 in TPL to match Arg-292 in AspAT, which binds the distal carboxylate group of substrates and is conserved among all known AspATs. Arg-100 in TPL was found to correspond to Thr-109 in AspAT, which interacts with the phosphate group of the coenzyme. The double mutation R100T/V283R of TPL increased the beta-elimination activity toward dicarboxylic amino acids at least 10(4)-fold. Dicarboxylic amino acids (L-aspartate, L-glutamate, and L-2-aminoadipate) were degraded to pyruvate, ammonia, and the respective monocarboxylic acids, e.g. formate in the case of L-aspartate. The activity toward L-aspartate (kcat = 0.21 s-1) was two times higher than that toward L-tyrosine. beta-Elimination and transamination as a minor side reaction (kcat = 0.001 s-1) were the only reactions observed. Thus, TPL R100T/V283R accepts dicarboxylic amino acids as substrates without significant change in its reaction specificity. Dicarboxylic amino acid beta-lyase is an enzyme not found in nature.
Combinatorial discovery of tumor targeting peptides using phage display (2003)

Peptides possess appropriate pharmacokinetic properties to serve as cancer imaging or therapeutic targeting agents. Currently, only a small number of rationally-derived, labeled peptide analogues that target only a limited subset of antigens are available. Thus, finding new cancer targeting peptides is a central goal in the field of molecular targeting. Novel tumor-avid peptides can be efficiently identified via affinity selections using complex random peptide libraries containing millions of peptides that are displayed on bacteriophage. In vitro and in situ affinity selections may be used to identify peptides with high affinity for the target antigen in vitro. Unfortunately, it has been found that peptides selected in vitro or in situ may not effectively target tumors in vivo due to poor peptide stability and other problems. To improve in vivo targeting, methodological combinatorial chemistry innovations allow selections to be conducted in the environment of the whole animal. Thus, new targeting peptides with optimal in vivo properties can be selected in vivo in tumor-bearing animals. In vivo selections have been proven successful in identifying peptides that target the vasculature of specific organs. In addition, in vivo selections have identified peptides that bind specifically to the surface of or are internalized into tumor cells. In the future, direct selection of peptides for cancer imaging may be expedited using genetically engineered bacteriophage libraries that encode peptides with intrinsic radiometal-chelation or fluorescent sequences.
Biological Selection of Peptides for Poly(l-lactide) Substrates (2008)

Short peptides that recognize the alpha form of poly( l-lactide) (PLLA) crystalline films were identified from a phage-displayed peptide library. An enzyme-linked immunosorbent assay (ELISA) revealed that the apparent binding constants of the phage clones for the alpha form of PLLA were greater than those of the unselected phage library. The specificity index for the alpha form of PLLA referred to a structurally similar atactic poly(methyl methacrylate) (at-PMMA), supporting the alpha form of PLLA specific binding of the selected phage. Amino acid residues with proton-donor lateral groups and hydrophobic alkyl groups were relatively enriched in a sequence of heptapeptides on the specific phage clones, thereby suggesting the presence of hydrogen bonding as well as hydrophobic interactions between the alpha form of PLLA and the peptides. Surface plasmon resonance (SPR) analysis revealed that the binding constant of the freed c22 heptapeptide (Gln-Leu-Met-His-Asp-Tyr-Arg) for the alpha form of PLLA was greater than those for reference at-PMMA, amorphous PLLA, and the beta form of PLLA. It was found that c22 peptide can recognize slight differences in PLLA polymorphs such as a crystalline state and an arrangement of PLLA functional groups.
The IC-SNURF-SNRPN transcript serves as a host for multiple small nucleolar RNA species and as an antisense RNA for UBE3A (2001)

The imprinted domain on human chromosome 15 consists of two oppositely imprinted gene clusters, which are under the coordinated control of an imprinting center (IC) at the 5' end of the SNURF-SNRPN gene. One gene cluster spans the centromeric part of this domain and contains several genes that are transcribed from the paternal chromosome only (MKRN3, MAGEL2, NDN, SNURF-SNRPN, HBII-13, HBII-85 and HBII-52). Apart from the HBII small nucleolar RNA (snoRNA) genes, each of these genes is associated with a 5' differentially methylated region (DMR). The second gene cluster maps to the telomeric part of the imprinted domain and contains two genes (UBE3A and ATP10C), which in some tissues are preferentially expressed from the maternal chromosome. So far, no DMR has been identified at these loci. Instead, maternal-only expression of UBE3A may be regulated indirectly through a paternally expressed antisense transcript. We report here that a processed antisense transcript of UBE3A starts at the IC. The SNURF-SNRPN sense/UBE3A antisense transcription unit spans more than 460 kb and contains at least 148 exons, including the previously identified IPW exons. It serves as the host for the previously identified HBII-13, HBII-85 and HBII-52 snoRNAs as well as for four additional snoRNAs (HBII-436, HBII-437, HBII-438A and HBII-438B), newly identified in this study. Almost all of those snoRNAs are encoded within introns of this large transcript. Northern blot analysis indicates that most if not all of these snoRNAs are indeed expressed by processing from these introns. As we have not obtained any evidence for other genes in this region, which, from the mouse data appears to be critical for the neonatal Prader-Willi syndrome phenotype, a lack of these snoRNAs may be causally involved in this disease.
Collagen oligomers modulate physical and biological properties of three‐dimensional self‐assembled matrices (2010)

Elucidation of mechanisms underlying collagen fibril assembly and matrix-induced guidance of cell fate will contribute to the design and expanded use of this biopolymer for research and clinical applications. Here, we define how Type I collagen oligomers affect in-vitro polymerization kinetics as well as fibril microstructure and mechanical properties of formed matrices. Monomers and oligomers were fractionated from acid-solubilized pig skin collagen and used to generate formulations varying in monomer/oligomer content or average polymer molecular weight (AMW). Polymerization half-times decreased with increasing collagen AMW and closely paralleled lag times, indicating that oligomers effectively served as nucleation sites. Furthermore, increasing AMW yielded matrices with increased interfibril branching and had no correlative effect on fibril density or diameter. These microstructure changes increased the stiffness of matrices as evidenced by increases in both shear storage and compressive moduli. Finally, the biological relevance of modulating collagen AMW was evidenced by the ability of cultured endothelial colony forming cells to sense associated changes in matrix physical properties and alter vacuole and capillary-like network formation. This work documents the importance of oligomers as another physiologically-relevant design parameter for development and standardization of polymerizable collagen formulations to be used for cell culture, regenerative medicine, and engineered tissue applications.
Generation of a Transgenic Mouse with Lung-specific Overexpression of the Human Interleukin-1 Receptor Antagonist Protein (1998)

The purpose of the studies described here was to test the hypothesis that overexpression of the human interleukin-1 receptor antagonist (IL-1ra) in the distal airway epithelia of mice would result in amelioration of the inflammatory effects of IL-1alpha. The coding region of the human IL-1ra gene was placed under transcriptional control of the 5' flanking region of the human SP-C gene. Transgenic mice were generated by pronuclear injection of the transgene and identified by Southern blot analysis of genomic DNA. RNA expression of the transgene was confirmed by Northern blot analysis. In order to determine whether expression of the transgene conferred protection against inflammatory stimuli, control and transgenic mice were treated with IL-1alpha by intratracheal instillation. Six hours after treatment, bronchoalveolar lavage was performed, which revealed a statistically significant decrease in the degree of neutrophilia in the transgenic mice as compared with control mice. Furthermore, there was a significant reduction in the whole-lung myeloperoxidase concentration. Reverse transcription-polymerase chain reaction analysis of whole-lung RNA revealed a significant reduction in the messenger RNA/beta-actin ratio of macrophage inflammatory protein-1alpha (MIP-1alpha) and MIP-2 in the transgenic animals as compared with controls. The results of these studies indicate that distal airway epithelial cell expression of human IL-1ra results in partial protection from IL-1alpha-induced airway inflammation and injury.
Induction of mouse IgG2a- and IgG3-dependent cellular cytotoxicity in human monocytic cells (U937) by immune interferon. (1984)

The effects of natural and recombinant human gamma-interferon (IFN-gamma) on mouse monoclonal antibody-dependent cellular cytotoxicity (ADCC) mediated by U937 human monocytic-like cells were examined. The efficiency of mouse monoclonal antibody of different isotypes in inducing ADCC was also compared. The number of receptors for the Fc portion of immunoglobulin G (IgG) (FcR) for mouse IgG2a and IgG3 on U937 cells, as detected by IgG antibody-sensitized erythrocyte rosette formation, was significantly enhanced by IFN-gamma. In contrast, FcR for mouse IgG1 and IgG2b were not detected even after IFN-gamma stimulation. U937 cell-mediated ADCC against sheep or ox red blood cell targets was minimal. However, after incubation with human purified IFN-gamma, U937 cells exhibited increased activity in IgG2a- and IgG3-dependent lysis, whereas their activity in IgG1- and IgG2b-dependent lysis was low. ADCC stimulated by IFN-gamma was inhibited by Protein A. When mouse peritoneal exudate cells were used, FcR for all IgG isotypes were easily detected, and all IgG isotypes mediated ADCC. Taken together, these results indicate that IFN-gamma induces U937 cell ADCC with mouse IgG2a and IgG3 partly through augmentation of FcR expression. Recombinant IFN-gamma showed the same effect as natural IFN-gamma. These effects of IFN-gamma were completely abrogated by anti-IFN-gamma serum but not by anti-IFN-alpha or normal rabbit serum. Addition of polymyxin B or lipopolysaccharide did not affect the activity of IFN-gamma.
Diffuse reflectance spectroscopy for ultraviolet A protection factor measurement: correlation studies between in vitro and in vivo measurements (2009)

This paper presents studies using the DRS technique to assess the UVA protection factor in different sunscreen formulae correlating with in vitro and in vivo PFA/PPD values. It is a fast method, non-invasive and does not involve any subject irradiation. The technique is a good estimator for the in vivo UVA protection factor as well as a way to assess, in vivo, the photostability of sunscreen formulation in the UVA.
4D video textures for interactive character appearance (2014)

Abstract 4D Video Textures (4DVT) introduce a novel representation for rendering video‐realistic interactive character animation from a database of 4D actor performance captured in a multiple camera studio. 4D performance capture reconstructs dynamic shape and appearance over time but is limited to free‐viewpoint video replay of the same motion. Interactive animation from 4D performance capture has so far been limited to surface shape only. 4DVT is the final piece in the puzzle enabling video‐realistic interactive animation through two contributions: a layered view‐dependent texture map representation which supports efficient storage, transmission and rendering from multiple view video capture; and a rendering approach that combines multiple 4DVT sequences in a parametric motion space, maintaining video quality rendering of dynamic surface appearance whilst allowing high‐level interactive control of character motion and viewpoint. 4DVT is demonstrated for multiple characters and evaluated both quantitatively and through a user‐study which confirms that the visual quality of captured video is maintained. The 4DVT representation achieves &gt;90% reduction in size and halves the rendering cost.
Identification and validation of cell surface antigens for antibody targeting in oncology (2004)

Recent clinical successes with antibodies have reinvigorated interest in the identification and validation of new antigens for antibody therapy, including cell surface proteins for targeting in oncology, the focus of this review. Target identification commonly involves the search for differences between tumor and non-tumor cell lines and/or tissue at the DNA, mRNA, protein or antibody reactivity levels. The next stage, target validation, utilizes antibodies to profile the expression of antigen in normal and tumor tissue and to verify that the antigen is selectively expressed on the surface of tumor cells. Supportive evidence for protein expression is often sought by mRNA profiling and, sometimes, analysis for genomic defects. Unfortunately, concordance between mRNA and protein levels has been found in only about approximately 20% of cases and therefore must be evaluated for individual targets of interest. Antigens judged suitable for antibody targeting are then advanced to the next stage, namely, in vitro and then in vivo screening of antibodies for anti-tumor activities. Subsequent optimization of an antibody clinical lead for therapy is a desirable, if not obligatory, step to developing an antibody as an anti-cancer therapeutic. No single approach or even combination of methods has emerged as the preferred way to identify surface antigens suitable for targeting in oncology. Major options at each step in the process are reviewed here, including their strengths and limitations.
End Points and United States Food and Drug Administration Approval of Oncology Drugs (2003)

End points other than survival were the approval basis for 68% (39 of 57) of oncology drug marketing applications granted regular approval and for all 14 applications granted accelerated approval from January 1, 1990, to November 1, 2002.
CORPORATE ACTIVITIES IN SPEECH RECOGNITION AND NATURAL LANGUAGE: ANOTHER "NEW SCIENCE"-BASED TECHNOLOGY (1999)

We have used data on patents and publications, and from an Internet-based survey, to analyse corporate technological activities in Automatic Speech Recognition (ASR) and Natural Language Processing (NLP) technologies. Two distinct clusters of firms exist: large firms mainly in telecommunications, desktop computing and consumer electronics; and small firms specialising in speech technologies. The small specialised firms depend heavily on nearby universities and public research institutes and, to some extent, on nearby large firms; their relations with the large firms are complementary as well as competitive. Similar patterns can be observed in other, recently emerging, "new science"-based technologies. Integration between ASR and NLP has so far been weak with the two research communities functioning more or less independently, with the former progressing more rapidly than the latter. Having built technological capabilities in ASR and NLP with a small proportion of their corporate technological resources, the large firms have two options depending on the rate of progress in these technologies (especially NLP) in the future. If it is high, substantial investments (including those in complementary technologies) could open up massive market opportunities. If it is low, modest investments will allow the exploitation of niche markets.
Spontaneous oligomerization of a staphylococcal alpha-hemolysin conformationally constrained by removal of residues that form the transmembrane beta-barrel (1997)

Staphylococcal alpha-hemolysin is a water soluble, monomeric, bacterial exotoxin, which forms heptameric pores in membranes. The rate determining step in assembly is the conversion of a heptameric prepore to the fully assembled pore in which the central glycine-rich domain of each subunit inserts into the membrane to form a 14 strand beta barrel. Barrel formation is accompanied by a conformational change in which each N terminus latches onto an adjacent subunit. In the monomer in solution, the central domain is loosely organized and exposed to solvent. In this study, 25 amino acids of the central domain were removed and replaced with the sequence Asp-Gly, which favors the formation of a type I' beta-turn, to yield a mutant devoid of hemolytic activity. Within minutes after synthesis in the absence of membranes, the mutant polypeptide spontaneously assembled into heptamers, as demonstrated by atomic force microscopy. Limited proteolysis suggested that the N termini of the subunits in the heptamers were in the fully assembled pore conformation rather than the prepore conformation. Based on these findings, the deletion is proposed to constrain the central domain and thereby force the creation of a shortened beta barrel, which in turn induces the additional structural changes that normally accompany pore formation. The truncated pore might make a useful framework for the construction of designed membrane active macromolecules.
The signal transducing photoreceptors of plants (2005)

Light signals are amongst the most important environmental cues regulating plant development. In addition to light quantity, plants measure the quality, direction and periodicity of incident light and use the information to optimise growth and development to the prevailing environmental conditions. Red and far-red wavelengths are perceived by the photoreversible phytochrome family of photoreceptors, whilst the detection of blue and ultraviolet (UV)-A wavelengths is conferred by the cryptochromes and phototropins. Higher plants contain multiple discrete phytochromes, the apoproteins of which are encoded by a small divergent gene family. In Arabidopsis, two cryptochrome and two phototropin family members have been identified and characterized. Photoreceptor action regulates development throughout the lifecycle of plants, from seed germination through to architecture of the mature plant and the onset of reproduction. The roles of individual photoreceptors in mediating plant development have, however, often been confounded by redundant, synergistic and in some cases mutually antagonistic mechanisms of action. The isolation of mutants null for individual photoreceptors and the construction of mutants null for multiple photoreceptors have therefore been paramount in elucidating photoreceptor functions. Photoreceptor action does not, however, operate in isolation from other signalling systems. The integration of light signals with other environmental cues enables plants to adapt their physiology to changing seasonal environments. This paper summarises current understanding of photoreceptor families and their functions throughout the lifecycle of plants. The integration of light signals with other environmental stimuli is also discussed.
The pneumococcal conjugate vaccine. (2002)

Streptococcus pneumoniae is the most frequent cause of otitis media, sinusitis, and pneumonia in children. It is also one of the most common causes of invasive bacterial infections in children including bacteremia and meningitis. One of the current issues regarding S. pneumoniae is the emergence of pneumococcal strains resistant to penicillin and other antibiotics. Children less than two years of age suffer an increased incidence of invasive pneumococcal disease but fail to respond to the 23-valent polysaccharide vaccine because of the immaturity of the T-cell independent immune function. Covalently conjugating the polysaccharide antigen to a carrier protein improves the immune response by permitting the host to utilize a T-cell dependent immune response that is adequately mature in children less than two years of age. Immunogenicity studies of the currently licensed heptavalent conjugated polysaccharide vaccine, (Prevnar, marketed by Wyeth Lederle Vaccines) demonstrated that infants vaccinated with three doses 2 months apart at 2, 4, and 6 months of age successfully developed antibodies to all 7 serotypes; booster doses at 12-15 months demonstrated an amnestic response for each serotype. Immunogenicity studies have similarly demonstrated successful responses in children with sickle cell disease and human immunodeficiency virus infection. An efficacy trial involving nearly 38,000 subjects demonstrated the vaccine's effectiveness in healthy children against invasive pneumococcal disease as well as against pneumonia and otitis media. Currently the US Advisory Committee on Immunization Practices (ACIP) recommends that all infants and children under 24 months of age receive the vaccine. The ACIP recommends that infants receive the vaccine routinely at 2, 4 and 6 months with a fourth dose at 12 to 15 months of age. Infants may receive the first dose as early as 6 weeks of age. The vaccine is also indicated for children 24 to 59 months of age who are at high risk for pneumococcal infection. Adverse events include local reactions in the first two days following vaccination such as approximately 10% reporting erythema, 10% induration, and 20% tenderness. Fever of 38 degrees C or higher occurred in 15% to 25% of children in the first two days following vaccination. Follow-up studies should address important questions regarding the use of pneumococcal conjugate vaccine and other age groups.