gebhart/patrepeval huggingface dataset:
The refined crystal structure of the 3C gene product from hepatitis A virus: specific proteinase activity and RNA recognition (1997)

The virally encoded 3C proteinases of picornaviruses process the polyprotein produced by the translation of polycistronic viral mRNA. The X-ray crystallographic structure of a catalytically active mutant of the hepatitis A virus (HAV) 3C proteinase (C24S) has been determined. Crystals of this mutant of HAV 3C are triclinic with unit cell dimensions a = 53.6 A, b = 53.5 A, c = 53.2 A, alpha = 99.1 degrees, beta = 129.0 degrees, and gamma = 103.3 degrees. There are two molecules of HAV 3C in the unit cell of this crystal form. The structure has been refined to an R factor of 0.211 (Rfree = 0.265) at 2.0-A resolution. Both molecules fold into the characteristic two-domain structure of the chymotrypsin-like serine proteinases. The active-site and substrate-binding regions are located in a surface groove between the two beta-barrel domains. The catalytic Cys 172 S(gamma) and His 44 N(epsilon2) are separated by 3.9 A; the oxyanion hole adopts the same conformation as that seen in the serine proteinases. The side chain of Asp 84, the residue expected to form the third member of the catalytic triad, is pointed away from the side chain of His 44 and is locked in an ion pair interaction with the epsilon-amino group of Lys 202. A water molecule is hydrogen bonded to His 44 N(delta1). The side-chain phenolic hydroxyl group of Tyr 143 is close to this water and to His 44 N(delta1) and may be negatively charged. The glutamine specificity for P1 residues of substrate cleavage sites is attributed to the presence of a highly conserved His 191 in the S1 pocket. A very unusual environment of two water molecules and a buried glutamate contribute to the imidazole tautomer believed to be important in the P1 specificity. HAV 3C proteinase has the conserved RNA recognition sequence KFRDI located in the interdomain connection loop on the side of the molecule diametrically opposite the proteolytic site. This segment of polypeptide is located between the N- and C-terminal helices, and its conformation results in the formation of a well-defined surface with a strongly charged electrostatic potential. Presumably, this surface of HAV 3C participates in the recognition of the 5' and 3' nontranslated regions of the RNA genome during viral replication.
A Mechanistic Study of the Hydrolytic Stability of Poly(2-(dimethylamino)ethyl methacrylate) (1998)

The hydrolytic stability of poly(2-(dimethylamino)ethyl methacrylate) was investigated and compared with the stability of its monomer 2-(dimethylamino)ethyl methacrylate (DMAEMA), with 2-(dimethylamino)ethyl isobutyrate (DMAEIB), representing the repeating unit in the polymer, and with the related 3-(dimethylamino)propyl methacrylate (DMAPMA) (H0/pH range −0.5 to +12, at 37 °C, in aqueous solution). At pH < 3, the unsaturated DMAEMA and DMAPMA were more stable than the saturated DMAEIB. At pH 4−8, DMAEMA and DMAEIB were equally stable, but less stable than DMAPMA. This has been ascribed to a coordination of the protonated dimethylamino group and the ester carbonyl, rendering the ester more susceptible to nucleophilic attack of a hydroxyl ion. At alkaline pH (>pKa) no differences in stability between the compounds were found. P(DMAEMA), either in its free form or complexed to DNA, was substantially more stable to hydrolytic degradation than DMAEMA and DMAEIB. Fluorescence measurements performed with a copolymer of DMAEMA and dansyl ethyl methacrylamide showed that the dielectric constant (εr) experienced in the environment of the polymer backbone, was low (about 7). This microenvironment might be the reason for the hydrolytic stability of the polymer, since the hydrolysis of the monomer decreased substantially with decreasing εr of the medium. Accelerated degradation (80 °C, pH 1 and 7) of p(DMAEMA) and poly(2-(dimethylamino)ethyl acrylate), p(DMAEA), showed that p(DMAEA) was more sensitive to hydrolysis. This can be explained by the assumption that, due to the lack of the methyl group, the εr in the environment of the acrylate backbone is higher than the εr in the environment of the p(DMAEMA) backbone.
Sustained Subconjunctival Protein Delivery Using a Thermosetting Gel Delivery System (2010)

Our findings suggest that the thermosetting gel system may be a feasible method for safe and convenient sustained delivery of proteins to choroidal and retinal tissue in the posterior segments of the eye.
Human factor VIIa and its complex with soluble tissue factor: evaluation of asymmetry and conformational dynamics by ultracentrifugation and fluorescence anisotropy decay methods (1993)

Ultracentrifugation and fluorescence anisotropy decay measurements were used to evaluate the asymmetry and conformational dynamics of human blood clotting enzyme VIIa (VIIa) and the complex it forms with a soluble truncation mutant of human tissue factor (sTF) which acts as an essential cofactor for VIIa. Sedimentation velocity experiments showed that both VIIa and the sTF.VIIa complex are highly asymmetric. In each case, the friction ratio f/fsphere, is consistent with a family of general elliposids ranging from prolate to oblate. Fluorescence anisotropy decay experiments were used to limit the family of elliposids which can describe the hydrodynamic behavior of VIIa and sTF.VIIa. For both VIIa and the sTF.VIIa complex, the oblate ellipsoid of revolution was eliminated. In addition, the fluorescence anisotropy decay data clearly show that upon binding sTF.VIIa loses a segmental motion involving a domain containing the active site of the enzyme. This suggests that sTF causes a stabilization of a limited range of VIIa conformations. This stabilization may be important for proper recognition of the TF.VIIa substrate, factor X.
Staphylococcus aureusantigens and challenges in vaccine development (2008)

Staphylococcus aureus is an important cause of nosocomial and community-acquired infections in humans and animals, as well as mastitis in dairy cattle. Methicillin-resistant S. aureus is increasingly recognized as a cause of staphylococcal infection and, therefore, immunotherapeutics have received new interest in both human and veterinary medicine. Vaccines aimed at preventing S. aureus infection in humans and mastitis in dairy cattle have been studied for many years. While some formulations have shown promise in ameliorating clinical disease, few, if any, of the S. aureus vaccines developed have adequately prevented new infection. The antigens targeted by S. aureus vaccines and potential reasons for the lack of success of vaccination against S. aureus are reviewed in this article.
Energy Evaluation for DC/DC Converters in DC-Based Wind Farms (2007)

In this thesis the suitability of three topologies for DC/DC converters in a DC wind farm grid is investigated from an energy efficiency and energy production cost point of view. The three selected topologies are the fullbridge converter, the single active bridge converter and the series parallel resonant converter. The losses are calculated for all three topologies as a function of the wind speed considering the losses in the semiconductor components and in the transformer. To obtain the average losses, the losses for each converter are integrated over the wind distribution for different average wind speeds.It is found that the resonant converter has the lowest losses of the three types for the DC wind farm application with power losses of about 2.0 - 2.5 % of the input power and the fullbridge converter has slightly higher losses with 2.3 - 3.5 % losses depending on the position in the wind turbine grid. The single active bridge converter has considerably higher losses than the other two topologies with 3.5 - 5.0 % losses. It is shown that the variable operating conditions create problems for all three converters, and as mentioned the single active bridge converter is most affected by the wide range of operation conditions. When comparing the resonant converter and the fullbridge converter, the fullbridge converter has a smaller transformer as well as lower peak current and peak voltage, but also a higher number of diode modules in the output bridge. Comparing the contribution to the energy production cost for the converters, the topology with the lowest contribution varies between the positions in the wind turbine grid. For some positions, the cost of the higher losses for the fullbridge converter are compensated by lower investment cost for the fullbridge converter compared to the resonant converter. Considering the resonant capacitor, the higher peak voltage and the variable frequency control for the resonant converter, the fullbridge converter is here found to be the most suitable choice for the wind farm application. A measurement verification is conducted for the fullbridge converter, and the result found is that the simulated waveforms and the calculated losses agree with the measured values.
Of Escherichia coli and Man: Understanding Glioma Resistance to Temozolomide Therapy (2009)

Our understanding of the human cellular response to DNA alkylating agents has its origin in a rich history of genetic experimentation in prokaryotic model systems, including the bacterium Escherichia coli. The recent clinical finding that chemotherapy with the DNA alkylating agent, temozolomide, improved survival in patients afflicted with malignant gliomas has heightened interests in translating this understanding into therapeutic strategies. Because the molecular responses to temozolomide and other DNA alkylating agents are similar between humans and many prokaryotes, insights garnered from bacterial genetics may facilitate such translation. Studies in both prokaryotic and human systems reveal that the cellular response to temozolomide involves a dynamic network of interacting pathways. Given this complexity, it is perhaps not surprising that any single genetic alteration may confer either sensitivity or resistance to temozolomide depending on the context of other interacting pathways. Thus, models of the cellular resistance to temozolomide should account for the network of interacting pathways rather than focusing on any single canonical pathway.
Facile Synthesis of Oxazoles Starting from Ketones (2003)

Abstract A new and efficient method for the preparation of 2,4- and 2,4,5-substituted oxazoles is described which is based upon the reaction of α-sulfonyloxy ketone intermediates with acetamide or benzamide.
Cryptococcus neoformans Promotes Its Transmigration into the Central Nervous System by Inducing Molecular and Cellular Changes in Brain Endothelial Cells (2013)

Cryptococcus spp. cause fungal meningitis, a life-threatening infection that occurs predominately in immunocompromised individuals. In order for Cryptococcus neoformans to invade the central nervous system (CNS), it must first penetrate the brain endothelium, also known as the blood-brain barrier (BBB). Despite the importance of the interrelation between C. neoformans and the brain endothelium in establishing CNS infection, very little is known about this microenvironment. Here we sought to resolve the cellular and molecular basis that defines the fungal-BBB interface during cryptococcal attachment to, and internalization by, the human brain endothelium. In order to accomplish this by a systems-wide approach, the proteomic profile of human brain endothelial cells challenged with C. neoformans was resolved using a label-free differential quantitative mass spectrometry method known as spectral counting (SC). Here, we demonstrate that as brain endothelial cells associate with, and internalize, cryptococci, they upregulate the expression of several proteins involved with cytoskeleton, metabolism, signaling, and inflammation, suggesting that they are actively signaling and undergoing cytoskeleton remodeling via annexin A2, S100A10, transgelin, and myosin. Transmission electronic microscopy (TEM) analysis demonstrates dramatic structural changes in nuclei, mitochondria, the endoplasmic reticulum (ER), and the plasma membrane that are indicative of cell stress and cell damage. The translocation of HMGB1, a marker of cell injury, the downregulation of proteins that function in transcription, energy production, protein processing, and the upregulation of cyclophilin A further support the notion that C. neoformans elicits changes in brain endothelial cells that facilitate the migration of cryptococci across the BBB and ultimately induce endothelial cell necrosis.
Reconstructing textured meshes from multiple range+rgb maps (2002)

The reconstruction of high-quality 3D models sampling both the shape and the surface reflection attribute is still a complex task. This papers contains new algorithms to integrate in a single texturemapped mesh the color info contained in either standard digital photos or RGB-enhanced range maps, minimizing redundancy and optimizing the color attribute representation. We enhance a previous solution [12] with: improved use of the available images, better color matching and computational efficiency. According to visibility computations and some heuristics, we subdivide the mesh in patches and assign to each patch a section of one of the input images. These image sections are packed in a texture image minimizing space but maintaining image coherence. Finally, we eliminate most of the color difference or discontinuity which exist in input images (applying a cross-correlation and interpolation between adjoining sections of the input images, directly on the texture image space). Note that this last step is performed on the whole texture, in contrast to others approaches that apply color smoothing just on small transition zones. 1
A human Hox 1 homeobox gene exhibits myeloid-specific expression of alternative transcripts in human hematopoietic cells (1991)

As part of a survey of the expression of homeobox-containing genes in human hematopoietic cells, we identified a novel gene (PL1) expressed only in cells of the myelomonocytic lineage (Shen et al., Proc. Natl. Acad. Sci, USA 86, 8536, 1989). On Northern gel analysis, major transcripts of 3.0 and 2.2 kb length are observed. Alternatively spliced homeobox-containing cDNAs, corresponding to the major transcripts, have been cloned from two myeloid leukemia cell libraries. The two cDNAs share the homeodomain and 3' flanking region but have unique 5' flanking regions. The longer transcript, would encode a 496 amino acid homeobox-containing protein, while the shorter message would encode a 94 amino acid homeobox-containing protein lacking the extended amino-terminal region. These two transcripts are differentially expressed in human leukemia cell lines. The larger transcript is exclusively expressed in cells with myelomonocytic features, while the smaller transcript is expressed in a variety of hematopoietic cell types. PL mRNA is also detectable in normal human bone marrow by RNAse protection. Neither transcript is expressed in uninduced teratocarcinoma cells or in the adult human tissues surveyed. The homeodomain is identical to the genomic sequence for Hox 1H, a newly identified member of the Hox 1 locus (Acampora et al. Nucl. Acids Res. 17, 10385, 1989). The PL1 gene was localized to chromosome 7 using chromosome specific blots and sublocalized to region pI4-21 by in situ hybridization of chromosomal spreads, confirming its location within the Hox 1 complex.
Co‐Stimulatory Blockade in the Treatment of Murine Systemic Lupus Erythematosus (SLE) (2003)

Although the life span of patients with systemic lupus erythematosus (SLE) has improved considerably over the last several decades, the toxicities of chronic immunosuppressive therapy are major causes of morbidity and mortality. Safer and more effective therapies for SLE are clearly needed. SLE is characterized by excessive activation of both B and T lymphocytes. Activation of these cells requires both antigen engagement and co-stimulatory signals from interacting lymphocytes (Carreno, B.M. M. Collins, 2002, Annu. Rev. Immunol. 20: 29-53; Grewal, I.S. R.A. Flavell, 1998, Annu. Rev. Immunol. 16: 111-135). Thus, blockade of co-stimulatory signals offers a new therapeutic approach to SLE. Our short-term goal has been to understand the effect of co-stimulatory blocking reagents on the development, selection, and activation of pathogenic anti-dsDNA antibody producing B cells in mice genetically pre-determined to develop SLE and showing signs of either early or advanced disease activity. Our long-term goal is to use the knowledge we gain to design therapeutic regimens for humans that avoid the complications of long-term immunosuppression. As new co-stimulatory molecules are discovered, studying their mechanism of action in animal models and their clinical utility in human autoimmune disease should lead both to a new understanding of disease pathogenesis and also to safer and more effective therapies.
New Bone Formation in Osteoporosis Following Treatment With Sodium Fluoride (1966)

O STEOSCLEROSIS associated with chronic fluoride exposure is well documented.<sup>1,2</sup>Sodium fluoride has been used experimentally in the treatment of Paget's disease of bone, osteogenesis imperfecta, multiple myeloma, and osteoporosis.<sup>3-7</sup>Clinical and metabolic results have been obtained in these patients but detailed microscopic data on the effects of fluoride treatment on the bone have not been reported. The present report describes a patient with ulcerative colitis and hepatic cholangiolitis who was treated with corticosteroids with subsequent appearance of osteoporosis and vertebral body collapse. Sodium fluoride therapy was instituted for the osteoporosis and because of the active ulcerative colitis and liver disease, the patient was continued on corticosteroids. The present study was undertaken to obtain clinical, metabolic, and histologic data on this patient who was treated simultaneously with sodium fluoride and corticosteroids. <h3>Report of a Case</h3> A 63-year-old, married, white female (SMH 13-15-97) entered the hospital because of diarrhea
Crystal Structure of the PAC1R Extracellular Domain Unifies a Consensus Fold for Hormone Recognition by Class B G-Protein Coupled Receptors (2011)

Pituitary adenylate cyclase activating polypeptide (PACAP) is a member of the PACAP/glucagon family of peptide hormones, which controls many physiological functions in the immune, nervous, endocrine, and muscular systems. It activates adenylate cyclase by binding to its receptor, PAC1R, a member of class B G-protein coupled receptors (GPCR). Crystal structures of a number of Class B GPCR extracellular domains (ECD) bound to their respective peptide hormones have revealed a consensus mechanism of hormone binding. However, the mechanism of how PACAP binds to its receptor remains controversial as an NMR structure of the PAC1R ECD/PACAP complex reveals a different topology of the ECD and a distinct mode of ligand recognition. Here we report a 1.9 Å crystal structure of the PAC1R ECD, which adopts the same fold as commonly observed for other members of Class B GPCR. Binding studies and cell-based assays with alanine-scanned peptides and mutated receptor support a model that PAC1R uses the same conserved fold of Class B GPCR ECD for PACAP binding, thus unifying the consensus mechanism of hormone binding for this family of receptors.
Cognitive radio as a mechanism to manage front-end linearity and dynamic range (2009)

Most of the consideration of the benefits and applicability of dynamic spectrum access has been focused on opportunities associated with spectrum availability. This article describes the use of DSA to resolve challenges in achieving wireless and cognitive radio operation in dense or energetic spectrum. It also demonstrates that the use of DSA can significantly reduce requirements for linearity and dynamic range in the radio front-end, and reduce the intermodulation induced noise floor through integration of DSA with the selection of front-end filter settings. This approach could enable DSA and cognitive radios to be more affordable than conventional radios, and addresses spectrum issues that are not practically manageable through manual approaches.
Bile Salt Hydrolase Activity in Probiotics (2006)

Probiotics are defined as “living microorganisms, which upon ingestion in certain numbers exert health benefits on the host beyond inherent basic nutrition” ([43][1]). Various studies have indicated that probiotics may alleviate lactose intolerance; have a positive influence on the intestinal
α‐Lipoic acid blocks HIV‐1 LTR‐dependent expression of hygromycin resistance in THP‐1 stable transformants (1996)

Gene expression of human immunodeficiency virus (HIV) depends on a host cellular transcription factors including nuclear factor-kappaB (NF-kappaB). The involvement of reactive oxygen intermediates (ROI) has been implicated as intracellular messengers in the inducible activation of NF-kappaB. In this study, we compared the efficacy of two antioxidants, alpha-lipoic acid (LA) and N-acetylcysteine (NAC), which are widely recognized NF-kappaB inhibitors. Here, we demonstrate that LA has a more potent activity in inhibiting NF-KappaB-mediated gene expression in THP-1 cells that have been stably transfected with a plasmid bearing a hygromycin B resistance gene under the control of HIV-1 long terminal repeat (LTR) promoter. The spontaneous activation of NF-kappaB in this cell culture system leads to expression of the hygromycin phosphotransferase gene hence rendering the cells resistance to hygromycin B. In this study, the effect of the test compounds against transcriptional activity of HIV-1 LTR was evaluated based on the degree of cellular toxicity due to the inhibitory activity on the expression of hygromycin B resistance gene in the presence of hygromycin B. We also found that 0.2 mM LA could cause 40% reduction in the HIV-1 expression from the TNF-alpha-stimulated OM 10.1, a cell line latently infected with HIV-1. On the other hand, 10 mM NAC was required to elicit the same effect. Furthermore, the initiation of HIV-1 induction by TNF-alpha was completely abolished by 1 mM LA. These findings confirm the involvement of ROI in NF-kappaB-mediated HIV gene expression as well as the efficacy of LA as a therapeutic regimen for HIV infection and acquired immunodeficiency syndrome (AIDS). Moreover, this study validates the applicability of our present assay system which we primarily designed for the screening of candidate drugs against HIV-1 gene expression.
A Universal Biocatalyst for the Preparation of Base- and Sugar-Modified Nucleosides via an Enzymatic Transglycosylation (2002)

The E. coli BMT-4D/1A cells have been selected according to Munch-Petersen et al. They carry two regulatory mutations (cytR and deoR) and are able to synthesize constitutively nucleoside-catabolizing enzymes, e.g., cells that possess high UPase and PNPase activities. The cells have been cross-linked by glutaraldehyde to afford a biocatalyst that retained high UPase and PNPase activities and was comfortable for repeated use. An incubation of 2′-deoxyguanosine (1) and 2-chloroadenine (2) (molar ratio 3 : 1) in K-phosphate buffer (10 mM; pH 7.0) in the presence of the biocatalyst at 65° for 7 h resulted in quantitative transformation of 2 into 2-chloro-2′-deoxyadenosine (4; cladribine) that was isolated in 81% yield (Scheme 1). Similarly, the reaction of guanosine (5) and 1,2,4-triazole-3-carboxamide (6) (molar ratio 1 : 1) in K-phosphate buffer (10 mM; pH 7.0) in the presence of the biocatalyst at 60° for 30 h led to the formation of 1-(β-D-ribofuranosyl)-1,2,4-triazole-3-carboxamide (8; ribavirin) in 90–92% yield (67–70% isolated yield) (Scheme 2).
Differential disappearance of inhibitory natural killer cell receptors during HAART and possible impairment of HIV-1-specific CD8 cytotoxic T lymphocytes (2001)

A decrease in CD3CD8iNKR cells is observed beyond 6 months of HAART. In some patients functional impairment due to LIR1/ILT2 expression may persist even after 24 months of successful HAART.