gebhart/patrepeval huggingface dataset:
1,2,3-Triazoles: structural changes on two effective inhibitors of the prostaglandin synthesis in vitro. (1989)

This paper describes the synthesis and the biological evaluation of some 1,2,3-triazoles which represent structural modifications of two compounds which are effective inhibitors of the prostaglandin synthesis in vitro. These modifications, concerning the elimination of the methylene bridge and/or the ether oxygen from the active molecules, show that every introduced structural changes caused a strong decrease of activity.
Uniform Vascular Contrast Enhancement and Reduced Contrast Medium Volume Achieved by Using Exponentially Decelerated Contrast Material Injection Method (2004)

Uniform vascular contrast enhancement and reduced contrast medium volume, which are desirable in CT angiography, can be achieved with exponentially decelerated injection.
Human RNA Helicase A Is a Lupus Autoantigen That Is Cleaved During Apoptosis (1999)

Proteolytic cleavage by caspases is the central event in cells undergoing apoptosis. Cleaved proteins are often targeted by autoantibodies, suggesting that the cleavage of self Ags enhances immunogenicity and is prone to induce an autoimmune response. We found autoantibodies that immunoprecipitated a 140-kDa RNA-associated protein, provisionally designated Pa, in 11 of 350 patient sera that were positive for antinuclear Abs in an immunofluorescence test. The Pa protein gave rise to three fragments with m.w. ranging from 120-130 kDa during anti-Fas-activated apoptosis. Pure caspase-3 cleaved the Pa protein into a 130-kDa fragment corresponding to the largest of these three products. Peptide sequence analysis of a tryptic digest from immunoaffinity-purified Pa showed 100% identity to human RNA helicase A (RHA). The identity of Pa with RHA was further confirmed by immunoblotting with rabbit anti-RHA Ab using anti-Pa immunoprecipitates as substrates. All 10 anti-RHA-positive patients who were clinically analyzed were diagnosed as having systemic lupus erythematosus, and 7 of them had lupus nephritis. RHA is a multifunctional protein with roles in cellular RNA synthesis and processing. Inactivation of RHA by cleavage may be an important part of the process leading to programmed cell death. The cleaved RHA fragments that are produced during apoptosis may trigger an autoimmune response in systemic lupus erythematosus.
Looking at proteins: representations, folding, packing, and design. Biophysical Society National Lecture, 1992 (2020)

Looking at proteins is an active process of interpretation and selection, emphasizing some features and deleting others. Multiple representations are needed, for such purposes as showing motions or conveying both the chain connectivity and the three-dimensional shape simultaneously. In studying and comparing protein structures, ideas are suggested about the determinants of tertiary structure and of folding (e.g., that Greek key beta barrels may fold up two strands at a time). The design and synthesis of new proteins "from scratch" provides a route toward the experimental testing of such ideas. It has also been a fruitful new perspective from which to look at structures, requiring such things as statistics on very narrowly defined structural categories and explicit attention to "negative design" criteria that actively block unwanted alternatives (e.g., reverse topology of a helix bundle, or edge-to-edge aggregation of beta sheets). Recently, the field of protein design has produced a rather unexpected general result: apparently we do indeed know enough to successfully design proteins that fold into approximately correct structures, but not enough to design unique, native-like structures. The degree of order varies considerably, but even the best designed material shows multiple conformations by NMR, more similar to a "molten globule" folding intermediate than to a well ordered native tertiary structure. In response to this conclusion, we are now working on systems that test useful questions with approximate structures (such as determining which factors most influence the choice of helix-bundle topology) and also analyzing how natural proteins achieve unique core conformations (e.g., for side chains on the interior side of a beta sheet, illustrated in the kinemages).
Evaluation of intestinal permeability in patients with inflammatory bowel disease using lactulose and measuring antibodies to lipid A. (1995)

This study looked at the intestinal permeability and the immune response to enteric bacterial antigens in patients with inflammatory bowel disease (IBD). They were evaluated by using a lactulose tolerance test and measuring blood anti-lipid A antibody concentrations, respectively. The lactulose tolerance tests were performed 22 times in 14 patients with Crohn's disease (CD), 19 times in 12 patients with ulcerative colitis (UC), and 12 times in 12 healthy controls. Blood lactulose concentrations were measured after oral administration every two hours for eight hours, also blood C reactive protein concentrations and anti-lipid A antibody concentrations were measured just before lactulose administration. Blood lactulose concentrations were significantly higher in patients with CD than in the controls from two to eight hours after administration, while in UC they were significantly higher than in the controls from six to eight hours. Maximum blood lactulose concentrations in each tolerance test in patients with the active phase significantly exceeded those in the inactive phase of either CD or UC. A significant correlation was also seen between the maximum blood lactulose concentrations and the C reactive protein concentrations. Blood anti-lipid A antibody concentrations in patients with CD were significantly higher than in the controls as well as in patients with UC in immunoglobulin (Ig) A class and IgG class. In UC they were significantly higher than in the controls in IgA class. But, they were not related to the severity of the disease of either CD or UC, and not correlated significantly with the maximum blood lactulose concentrations in either CD or UC. The intestinal permeability and the immune response to enteric bacterial antigens in patients with inactive CD were significantly increased over those in the controls as well as in patients with inactive UC. These findings suggest that an increase of the intestinal permeability and that of producing antibodies to enteric bacterial antigens are both important for the pathogenesis of IBD, and that the characteristics of CD and UC differ.
Image-guided radiovirotherapy for multiple myeloma using a recombinant measles virus expressing the thyroidal sodium iodide symporter (2003)

The Edmonston vaccine strain of measles virus (MV-Edm) propagates efficiently in a broad range of human tumor cells, killing them selectively. However, the oncolytic potency of MV-Edm in different human tumor xenograft therapy models is highly variable and there is no convenient way to map the distribution of virus-infected tissues in vivo. To enhance the oncolytic potency of MV-Edm against radiosensitive malignancies and to facilitate noninvasive imaging of infected tissues, we generated a recombinant MV-Edm encoding the human thyroidal iodide symporter (NIS). MV-NIS replicated almost as efficiently as unmodified MV-Edm, and human tumor cells efficiently concentrated radioiodine when infected with MV-NIS. Intratumoral spread of MV-NIS was noninvasively demonstrated by serial gamma-camera imaging of iodine-123 (123I) uptake both in MV-sensitive KAS-6/1 myeloma xenografts, which regressed completely after a single intravenous dose of MV-NIS, and in MM1 myeloma xenografts, which were unresponsive to MVNIS therapy. However, MV-resistant MM1 tumors regressed completely when 131I was administered 9 days after a single intravenous injection of MV-NIS (radiovirotherapy). 131I alone had no effect on MM1 tumor growth. While the potential hematopoietic toxicity of this new therapy requires further evaluation, image-guided radiovirotherapy is a promising new approach to the treatment of multiple myeloma, an incurable but highly radiosensitive plasma cell malignancy. Testing in other radiosensitive cancers is warranted.
Islet cell hyperexpression of HLA class I antigens: a defining feature in type 1 diabetes (2016)

Islet cell HLA class I hyperexpression is not an artefact, but is a hallmark in the immunopathogenesis of type 1 diabetes. The response is closely associated with elevated expression of STAT1 and, together, these occur uniquely in patients with type 1 diabetes, thereby contributing to their selective susceptibility to autoimmune-mediated destruction.
DNA sequences of the cysK regions of Salmonella typhimurium and Escherichia coli and linkage of the cysK regions to ptsH (1988)

Nucleotide sequences of the cysK regions of Salmonella typhimurium and Escherichia coli have been determined. A total of 3,812 and 2,595 nucleotides were sequenced from S. typhimurium and E. coli, respectively. Open reading frames of 323 codons were found in both species and were identified as those of cysK by comparison of deduced amino acid sequences with amino- and carboxyl-terminal amino acid analyses of the S. typhimurium cysK gene product O-acetylserine (thiol)-lyase A. The two cysK DNA sequences were 85% identical, and the deduced amino acid sequences were 96% identical. The major transcription initiation sites for cysK were found to be virtually identical in the two organisms, by using primer extension and S1 nuclease protection techniques. The -35 region corresponding to the major transcription start site was TTCCCC in S. typhimurium and TTCCGC in E. coli. The deviation of these sequences from the consensus sequence TTGACA may reflect the fact that cysK is subject to positive control and requires the cysB regulatory protein for expression. Sequences downstream of cysK were found to include ptsH and a portion of ptsI, thus establishing the exact relationship of cysK with these two genes. A 290-codon open reading frame, which may represent the cysZ gene, was identified upstream of cysK.
Home monitoring of sleep with a temporary-tattoo EEG, EOG and EMG electrode array: a feasibility study (2018)

The new system has great potential in monitoring sleep disorders in the home environment. Specifically, it may allow the identification of disorders associated with neurological disorders such as rapid eye movement (REM) sleep behavior disorder.
Spatially Sparse Precoding in Millimeter Wave MIMO Systems (2014)

Millimeter wave (mmWave) signals experience orders-of-magnitude more pathloss than the microwave signals currently used in most wireless applications and all cellular systems. MmWave systems must therefore leverage large antenna arrays, made possible by the decrease in wavelength, to combat pathloss with beamforming gain. Beamforming with multiple data streams, known as precoding, can be used to further improve mmWave spectral efficiency. Both beamforming and precoding are done digitally at baseband in traditional multi-antenna systems. The high cost and power consumption of mixed-signal devices in mmWave systems, however, make analog processing in the RF domain more attractive. This hardware limitation restricts the feasible set of precoders and combiners that can be applied by practical mmWave transceivers. In this paper, we consider transmit precoding and receiver combining in mmWave systems with large antenna arrays. We exploit the spatial structure of mmWave channels to formulate the precoding/combining problem as a sparse reconstruction problem. Using the principle of basis pursuit, we develop algorithms that accurately approximate optimal unconstrained precoders and combiners such that they can be implemented in low-cost RF hardware. We present numerical results on the performance of the proposed algorithms and show that they allow mmWave systems to approach their unconstrained performance limits, even when transceiver hardware constraints are considered.
1828–1838 (2012)

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Preclinical and Clinical Studies of MMP Inhibitors in Cancer (1999)

The role of matrix metalloproteinases in tumor angiogenesis and growth is now well recognized for models of both human and animal cancer. Clinical studies currently under way with the prototype matrix metalloproteinase inhibitor, marimastat, will establish whether inhibitors of these enzymes are of benefit in the treatment of different types of human cancer. On chronic therapy in humans, marimastat induces a reversible tendinitis that can also be detected in certain animal species. This paper compares the ability of broad-spectrum and various types of selective matrix metalloproteinase inhibitors to induce tendinitis and to exhibit anticancer effects in an animal cancer model. Under conditions in which both systemic exposure and inhibitor potency are controlled, selective inhibitors are less pro-tendinitic, but are weaker anticancer agents than broad-spectrum agents such as marimastat. The clinical relevance of these findings is discussed.
Solution of impedance matrix localization form of moment method problems in five iterations (1995)

The impedance matrix localization (IML) method replaces the usual full N × N moment method matrix by a sparse N × N matrix. Typically, this matrix has about 50 N nonzero elements. Iterative methods require one (or a few) matrix vector product(s) at each iteration. Each product can be accomplished in 50 N operations rather than N 2 for the usual moment method. There is a correspondence between the clumps of large numbers in the IML matrix and terms with a ray description such as in geometrical optics and the geometrical theory of diffraction. It is known that using these methods approximate solutions are possible while taking into account only a limited number of multiple interactions. Using this analogy an approximate factored form of the IML matrix is generated by explicitly using only a limited number of direct interactions. However, all multiple interactions involving these direct interactions are (implicitly) taken into account. This effectively gives an approximate inverse which is used in an iterative approach. A reduction in the residual of orders of magnitude per iteration is achieved. The result is a more accurate solution than was possible before and which requires only a few iterations. This method is generally applicable since the factored form is based on the structure of the IML matrix and not on any specific geometry.
Cathepsin L inactivates alpha 1-proteinase inhibitor by cleavage in the reactive site region. (1986)

The lysosomal cysteine proteinases cathepsin L and cathepsin B were examined for their effect on the neutrophil elastase inhibitory activity of human alpha 1-proteinase inhibitor (alpha 1PI). Human cathepsin L catalytically inactivated human alpha 1PI by cleavage of the bonds Glu354-Ala355 and Met358-Ser359 (the serine proteinase inhibitory site). Cathepsin B did not inactivate alpha 1PI, even when equimolar amounts of enzyme were employed. Cathepsin L is the first human proteinase shown to catalytically inactivate alpha 1PI. These findings, in conjunction with other reports, suggest that alpha 1PI contains a proteolytically sensitive region encompassing residues 350-358. Taken together with the discovery of the elastinolytic activity of cathepsin L (Mason, R. W., Johnson, D. A., Barrett, A. J., and Chapman, H. A. (1986) Biochem. J. 233, 925-927), the present findings emphasize the possible importance of cathepsin L in the pathological proteolysis of elastin and diminish the role that can be attributed to cathepsin B in such processes.
A novel hybrid seed system for plants (2007)

A two-component hybrid seed system has been developed that is broadly applicable and provides for effective generation and maintenance of the male-sterile parent, hybrid seed production and full restoration of fertility in the hybrid seed. The technology is based on the functional interaction of two loci that are inserted in the same position on two homologous chromosomes, and thus are 'linked in repulsion', and that jointly code for male sterility and herbicide resistance, both traits being expressed in heterozygous plants only. The localization to the same locus on a chromosome is achieved by the genetic transformation of plants with a construct containing both genetic elements (loci), and subsequent derivatization from the primary pro-locus of the two precursor lines using site-specific deletions. The functional interaction of the two loci is achieved through intein-based trans-splicing of two pairs of complementary protein fragments that provide for male sterility and herbicide resistance. Unlike the hybrid seed systems that are currently in use, the technology relies on the genetic modification of just one parent, and is therefore much simpler to develop and use. Arabidopsis has been used for the proof of principle presented here, but the essential elements of the technology are generic and have been shown to work in many crop species.
Characterization of biofilm and encrustation on ureteric stents in vivo (1994)

The results indicate that polyurethane is readily encrusted and colonized by bacteria in vivo despite antibiotic prophylaxis. Newer materials must be sought if effective long-term stenting is to be achieved.
A stop codon polymorphism of Toll-like receptor 5 is associated with resistance to systemic lupus erythematosus (2005)

Systemic lupus erythematosus (SLE) is an autoimmune disease with a complex genetic basis that includes susceptibility gene(s) within the chromosome 1q41-1q42 region. Toll-like receptor 5 (TLR5), the innate immune receptor for bacterial flagellin, maps to chromosome 1q41 and contains a common stop codon polymorphism that abrogates signaling (allele C1174T) and is associated with an increased risk of infection. By using transmission disequilibrium testing in a cohort containing 199 affected patients and their 75 unaffected siblings and 326 parents, we found that allele 1174C, but not 1174T (with the stop codon), was preferentially transmitted to SLE-affected offspring (a 19:6 transmitted/not transmitted ratio, P = 0.009). In contrast, the alleles of the other three TLR5 SNPs did not exhibit preferential transmission. In addition, we found that allele 1174C was not preferentially transmitted to unaffected offspring (3:6 transmitted/not transmitted ratio, P value not significant). The allele frequency of 1174T in the probands was 3.2% compared with 5.8% in unaffected individuals, which was consistent with a protective association (odds ratio, 0.51; 95% confidence interval, 0.26-0.98; P = 0.041). Subjects with the TLR5 stop codon produced significantly lower levels of proinflammatory cytokines in comparison with individuals with the wild-type genotype. Together, these results indicate that the TLR5 stop codon polymorphism is associated with protection from the development of SLE. These data support a role for flagellated bacteria and the innate immune response in the development of SLE with implications for novel immunomodulatory treatment strategies.
Characterization of (??)-bufuralol hydroxylation activities in liver microsomes of Japanese and Caucasian subjects genotyped for CYP2D6 (2001)

Twenty-four genetic polymorphisms in the CYP2D6 gene were analysed in liver DNA samples of 39 Japanese and 44 Caucasians and compared with CYP2D6 protein levels and bufuralol 1'- and 6-hydroxylation activities in liver microsomes of these human samples. We detected 13 types of CYP2D6 genetic polymorphisms and classified these into 20 genotypes; nine types were found in Japanese and 14 types in Caucasian samples. CYP2D6*10B, but not CYP2D6*10A, was the most frequent (34.6%) in Japanese. In Caucasians, several CYP2D6 polymorphisms including CYP2D6*4, *4D, *4E, *4L, *3, *9, *5 and *2E (frequencies of 6.8, 3.4, 4.5, 9.1, 1.1, 2.3, 2.3 and 4.5%, respectively) were detected. A Caucasian having CYP2D6*3/*5 had a protein with slower gel mobility (immunoblotting with anti-CYP2D6 antibody) and very low activity for bufuralol 1'-hydroxylation. Five Caucasian samples (CYP2D6*4/*4, *4/*4L, or *4D/*4L) had no measurable CYP2D6 protein and very low bufuralol 1'-hydroxylation activities. Seven Japanese subjects with CYP2D6*10B/*10B had CYP2D6 protein at levels of approximately 20% of those present in humans with CYP2D6*1 and *2 and catalysed bufuralol 1'-hydroxylation at low rates. Kinetic analysis of bufuralol 1'- and 6-hydroxylation indicates that (i) the Km values for 1'-hydroxylation were lower in individuals with CYP2D6*1/*1, *1/*2, *1/*2X2, and *2/*2 than those with CYP2D6*4/*4, *4/*4L, *4D/*4L, or *10B/*10B and Vmax values tended to be higher in the former groups (*1, *2), and (ii) individuals with heterozygous CYP2D6*1/*4D, *1/*4L, and *1/*5 had relatively high Vmax/Km ratios, whereas individuals with heterozygous CYP2D6*1/*9, *2/4D, *2/*5, *2/*10B, *2E/*4E, *3/*5, *4L/*9, and *10B/*39 had lower Vmax/Km ratios for bufuralol 1'-hydroxylation. Quinidine inhibited bufuralol 1'-hydroxylation in liver microsomes, particularly at low substrate concentrations, in individuals with CYP2D6*1/*1, and 1/1*2, but not those with CYP2D6*4/*4 and very slightly in individuals with CYP2D6*10B/*10B. The latter two groups were found to be more sensitive to alpha-naphthoflavone than the former groups, indicative of the contribution of CYP1A2. These results support the view that CYP2D6*3, *4, *4D, and *4L are major genotypes producing poor metabolizer phenotypes in CYP2D6 in Caucasians, whereas CYP2D6*10B is a major factor in decreased CYP2D6 protein expression and catalytic activities in Japanese.
The Oncogenic Capacity of HRX-ENL Requires the Transcriptional Transactivation Activity of ENL and the DNA Binding Motifs of HRX (1998)

The HRX gene (also called MLL, ALL-1, and Htrx) at chromosome band 11q23 is associated with specific subsets of acute leukemias through translocations that result in its fusion with a variety of heterologous partners. Two of these partners, ENL and AF9, code for proteins that are highly similar to each other and as fusions with HRX induce myeloid leukemias in mice as demonstrated by retroviral gene transfer and knock-in experiments, respectively. In the present study, a structure-function analysis was performed to determine the molecular requirements for in vitro immortalization of murine myeloid cells by HRX-ENL. Deletions of either the AT hook motifs or the methyltransferase homology domain of HRX substantially impaired the transforming effects of HRX-ENL. The methyltransferase homology domain was shown to bind non-sequence specifically to DNA in vitro, providing evidence that the full transforming activity of HRX-ENL requires multiple DNA binding structures in HRX. The carboxy-terminal 84 amino acids of ENL, which encode two predicted helical structures highly conserved in AF9, were necessary and sufficient for transformation when they were fused to HRX. Similarly, mutations that deleted one or both of these conserved helices completely abrogated the transcriptional activation properties of ENL. This finding correlates, for the first time, a biological function of an HRX fusion partner with the transforming activity of the chimeric proteins. Our studies support a model in which HRX-ENL induces myeloid transformation by deregulating subordinate genes through a gain of function contributed by the transcriptional effector properties of ENL.