gebhart/patrepeval huggingface dataset:
Identification and Characterization of Asporin (2001)

Asporin, a novel member of the leucine-rich repeat family of proteins, was partially purified from human articular cartilage and meniscus. Cloning of human and mouse asporin cDNAs revealed that the protein is closely related to decorin and biglycan. It contains a putative propeptide, 4 amino-terminal cysteines, 10 leucine-rich repeats, and 2 C-terminal cysteines. In contrast to decorin and biglycan, asporin is not a proteoglycan. Instead, asporin contains a unique stretch of aspartic acid residues in its amino-terminal region. A polymorphism was identified in that the number of consecutive aspartate residues varied from 11 to 15. The 8 exons of the human asporin gene span 26 kilobases on chromosome 9q31.1-32, and the putative promoter region lacks TATA consensus sequences. The asporin mRNA is expressed in a variety of human tissues with higher levels in osteoarthritic articular cartilage, aorta, uterus, heart, and liver. The deduced amino acid sequence of asporin was confirmed by mass spectrometry of the isolated protein resulting in 84% sequence coverage. The protein contains an N-glycosylation site at Asn(281) with a heterogeneous oligosaccharide structure and a potential O-glycosylation site at Ser(54). The name asporin reflects the aspartate-rich amino terminus and the overall similarity to decorin.
A Fast Computational Algorithm for the Discrete Cosine Transform (1977)

A Fast Discrete Cosine Transform algorithm has been developed which provides a factor of six improvement in computational complexity when compared to conventional Discrete Cosine Transform algorithms using the Fast Fourier Transform. The algorithm is derived in the form of matrices and illustrated by a signal-flow graph, which may be readily translated to hardware or software implementations.
Functional delivery of synthetic naked siRNA to the human trabecular meshwork in perfused organ cultures. (2007)

Readily available siRNA can be delivered to the intact human trabecular meshwork by intracameral perfusion. The delivered naked siRNA is functional, inhibiting not only the targeted gene but also their downstream effectors. This functional intracameral delivery might be of use to protect the trabecular meshwork from unwanted insults and could have important therapeutic applications.
Umsetzungen substituierter Aldehyde mit Diazoalkanen, IV1) Reaktionen von monosubstituierten Benzaldehyden mit Diazomethan (1976)

Abstract Durch stufenweise Umsetzung von 2 Moläquivv. o ‐Cyan‐ bzw. o ‐Chlorbenzaldehyd 1 mit Diazomethan entstehen neben 7b die Ketone 3a, b und die β‐Ketole 4a, b . Während 4a zum Chalkon 5 isomerisiert, dehydratisiert 4b zum Chalkon 6b . Die meta ‐substituierten Benzaldehyde 13 geben mit Diazomethan im Molverhältnis 2:1 die Ketone 14a, b , die Epoxide 15a, b und die β‐Ketole 16a, b ; die letzteren werden mit Acetanhydrid zu den Chalkonen 17a, b dehydratisiert. Die para ‐substituierten Benzaldehyde 21 lieferten mit einem halben Moläquiv. Diazomethan überwiegend die Ketone 24a, b und β‐Ketole 22a, b neben kleinen Mengen von Oxiran 25a , homologem β‐Ketol 27b und p ‐Cyanphenylaceton 26a . Aus äquivalenten Mengen Diazomethan und den äquivalenten Mengen zweier verschiedener Aldehyde (o,m,p‐Cyanbenzaldehyde und Chloral bzw. p‐Nitrobenzaldehyd) erhält man die “gemischten” β‐Ketole 9, 12, 19, 29 sowie die Oxirane 20, 30 neben den “einheitlichen” β‐Ketolen 4a, 11, 16a, 22a und anderen Ketonen.
Cysteinyl‐leukotrienes and their receptors in asthma and other inflammatory diseases: Critical update and emerging trends (2006)

Cysteinyl-leukotrienes (cysteinyl-LTs), that is, LTC4, LTD4, and LTE4, trigger contractile and inflammatory responses through the specific interaction with G protein-coupled receptors (GPCRs) belonging to the purine receptor cluster of the rhodopsin family, and identified as CysLT receptors (CysLTRs). Cysteinyl-LTs have a clear role in pathophysiological conditions such as asthma and allergic rhinitis (AR), and have been implicated in other inflammatory conditions including cardiovascular diseases, cancer, atopic dermatitis, and urticaria. Molecular cloning of human CysLT1R and CysLT2R subtypes has confirmed most of the previous pharmacological characterization and identified distinct expression patterns only partially overlapping. Interestingly, recent data provide evidence for the immunomodulation of CysLTR expression, the existence of additional receptor subtypes, and of an intracellular pool of CysLTRs that may have roles different from those of plasma membrane receptors. Furthermore, genetic variants have been identified for the CysLTRs that may interact to confer risk for atopy. Finally, a crosstalk between the cysteinyl-LT and the purine systems is being delineated. This review will summarize and attempt to integrate recent data derived from studies on the molecular pharmacology and pharmacogenetics of CysLTRs, and will consider the therapeutic opportunities arising from the new roles suggested for cysteinyl-LTs and their receptors.
Design of balanced and constant weight codes for VLSI systems (1998)

A constant weight, w, code with k information bits and r check bits is a binary code of length n=k+r and cardinality 2/sup k/ such that the number of 1s in each code word is equal to w. When w=[n/2], the code is called balanced. This paper describes the design of balanced and constant weight codes with parallel encoding and parallel decoding. Infinite families of efficient constant weight codes are given with the parameters k, r, and the "number of balancing functions used in the code design," /spl rho/. The larger /spl rho/ grows, the smaller r will be; and the codes can be encoded and decoded with VLSI circuits whose sizes and depths are proportional to pk and log/sub 2/ p, respectively. For example, a design is given for a constant weight w=33 code with k=64 information bits, r=10 check bits, and p=8 balancing functions. This code can be implemented by a VLSI circuit using less than 4,054 transistors with a depth of less than 30 transistors.
Rapid generation of mouse models with defined point mutations by the CRISPR/Cas9 system (2014)

Introducing a point mutation is a fundamental method used to demonstrate the roles of particular nucleotides or amino acids in the genetic elements or proteins, and is widely used in in vitro experiments based on cultured cells and exogenously provided DNA. However, the in vivo application of this approach by modifying genomic loci is uncommon, partly due to its technical and temporal demands. This leaves many in vitro findings un-validated under in vivo conditions. We herein applied the CRISPR/Cas9 system to generate mice with point mutations in their genomes, which led to single amino acid substitutions in proteins of interest. By microinjecting gRNA, hCas9 mRNA and single-stranded donor oligonucleotides (ssODN) into mouse zygotes, we introduced defined genomic modifications in their genome with a low cost and in a short time. Both single gRNA/WT hCas9 and double nicking set-ups were effective. We also found that the distance between the modification site and gRNA target site was a significant parameter affecting the efficiency of the substitution. We believe that this is a powerful technique that can be used to examine the relevance of in vitro findings, as well as the mutations found in patients with genetic disorders, in an in vivo system.
Molecular Identification of Aggrus/T1α as a Platelet Aggregation-inducing Factor Expressed in Colorectal Tumors (2003)

Platelets play an important role in hemostasis, thrombosis, and antimicrobial host defense and are also involved in the induction of inflammation, tissue repair, and tumor metastasis. We have previously characterized the platelet aggregation-inducing sialoglycoprotein (Aggrus/gp44) overexpressed on the surface of tumor cells. Because a platelet aggregation-neutralizing 8F11 monoclonal antibody that could specifically recognize Aggrus suppressed tumor-induced platelet aggregation, we have previously purified Aggrus by 8F11-affinity chromatography and found that purified Aggrus possessed the ability to induce aggregation of platelets. Here we show that Aggrus is identical to the T1alpha/gp38P/OTS-8 antigen, the function of which in tumors is unknown. Expression of mouse Aggrus and its human homologue (also known as T1alpha-2/gp36) induced platelet aggregation without requiring plasma components. Using the 8F11 antibody, we identified the highly conserved platelet aggregation-stimulating domain with putative O-glycosylated threonine residues as the critical determinant for exhibiting platelet aggregation-inducing capabilities. We compared the expression level of human aggrus mRNA using an array containing 160 cDNA pair samples derived from multiple human tumorigenic and corresponding normal tissues from individual patients. We found that expression level of aggrus was enhanced in most colorectal tumor patients. To confirm the protein expression, we generated anti-human Aggrus polyclonal antibodies. Immunohistochemical analysis revealed that Aggrus expression was frequently up-regulated in colorectal tumors. These results suggest that Aggrus/T1alpha is a newly identified, platelet aggregation-inducing factor expressed in colorectal tumors.
Oncogenes and Cancer (2008)

This review — the first in a series concerning the biology of cancer — is a comprehensive survey of oncogenes, tumor-suppressor genes, and microRNA genes in cancer cells. Work on the recently discovered microRNA genes in malignant cells has revealed new complexities in the regulation of oncogenes and tumor-suppressor genes and new opportunities for the treatment of cancer.
Substrate Properties of Fluorescent Ribonucleotides in the Terminal Transferase-Catalyzed Labeling of DNA Sequencing Primers (1996)

Terminal deoxynucleotidyltransferase (terminal transferase, E.C. 2.7.7.31) has been used to add a single fluorescent ribonucleotide to the 3' terminus of DNA sequencing primers, thereby creating primers suitable for automated DNA sequence analysis. The previously introduced procedure using fluorescein-UTP for the postsynthetic labeling of primers can, under appropriate reaction conditions, now be extended to commercially available fluorescein-ATP and fluorescein-CTP permitting greater flexibility in primer design. The products of these addition reactions have been shown to provide sequence data qualitatively and quantitatively identical to those obtained with conventional 5'-terminally labeled primers using cycle sequencing conditions in conjunction with an automated sequencer. Ribonucleotide derivatives of four other dyes (coumarin, tetramethylrhodamine, lissamine and Texas Red) were also examined for their potential in the terminal transferase-catalyzed reaction. Whereas coumarin-UTP was efficiently incorporated giving a monoaddition product, the conjugates of all other dyes with ATP, CTP and UTP were extremely poor substrates under all conditions tested.
Synthesis of 3-Aryl- and 3-Heteroaryl-7-azaindoles (1999)

The synthesis of 1-protected 3-trimethylstannyl-7-azaindoles and their coupling with aryl and heteroaryl halides is described.
Factors influencing the outcome of infectious bronchitis vaccination and challenge experiments (2014)

The factors influencing the outcome of infectious bronchitis vaccination and challenge experiments regarding the respiratory and renal systems are reviewed. Advantages and disadvantages of the available techniques for measuring protection against an infectious bronchitis virus challenge are discussed, including the definition of protection itself. Suggestions are made regarding some ways in which progress towards standardization of a recognized protocol for performing experimental challenge studies can be made and areas where more work is needed are indicated.
The MRP4/ABCC4 Gene Encodes a Novel Apical Organic Anion Transporter in Human Kidney Proximal Tubules (2002)

The cyclic nucleotides cAMP and cGMP play key roles in cellular signaling and the extracellular regulation of fluid balance. In the kidney, cAMP is excreted across the apical proximal tubular membrane into urine, where it reduces phosphate reabsorption through a dipyridamole-sensitive mechanism that is not fully understood. It has long been known that this cAMP efflux pathway is dependent on ATP and is inhibited by probenecid. However, its identity and whether cGMP shares the same transporter have not been established. Here the expression, localization, and functional properties of human multidrug resistance protein 4 (MRP4) are reported. MRP4 is localized to the proximal tubule apical membrane of human kidney, and membrane vesicles from Sf9 cells expressing human MRP4 exhibit ATP-dependent transport of [(3)H]cAMP and [(3)H]cGMP. Both probenecid and dipyridamole are potent MRP4 inhibitors. ATP-dependent [(3)H]methotrexate and [(3)H]estradiol-17beta-D-glucuronide transport by MRP4 and interactions with the anionic conjugates S-(2,4-dinitrophenyl)-glutathione, N-acetyl-(2,4-dinitrophenyl)-cysteine, alpha-naphthyl-beta-D-glucuronide, and p-nitrophenyl-beta-D-glucuronide are also demonstrated. In kidneys of rats deficient in the apical anionic conjugate efflux pump Mrp2, Mrp4 expression is maintained at the same level. It is concluded that MRP4 is a novel apical organic anion transporter and the putative efflux pump for cAMP and cGMP in human kidney proximal tubules.
Nononcogenic Retrovirus Infections as Models for Chronic and Relapsing Human Diseases: Introduction (1985)

Nononcogenic Retrovirus Infections as Models for Chronic and Relapsing Human Diseases: Introduction Get access Richard T. Johnson Richard T. Johnson Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, Maryland Please address requests for reprints to Dr. Richard T. Johnson, Department of Neurology, The Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, Maryland 21205. Search for other works by this author on: Oxford Academic PubMed Google Scholar Reviews of Infectious Diseases, Volume 7, Issue 1, January 1985, Pages 66–67, https://doi.org/10.1093/clinids/7.1.66 Published: 01 January 1985
Sjögren’s syndrome: a review of aetiology, pathogenesis, diagnosis and management (2010)

Sjögren's syndrome is a chronic autoimmune disease that affects many individuals within the community. Despite this, its exact aetiology and pathogenesis is still unclear. Sjögren's syndrome affects many organ systems in the body. However, for dental practitioners it is important to recognize the many oral and dental manifestations that are associated with the syndrome. In addition to these oral manifestations, this review will discuss the systemic manifestations of Sjögren's syndrome as well as the current understanding of factors that have a role in its aetiology and pathogenesis. Furthermore, this review will highlight the difficulties and complexities that are inherent in the diagnosis of Sjögren's syndrome and the important role that dental practitioners can play in the management of its oral manifestations. The effective management of oral manifestations and minimization of oral disease in patients with Sjögren's syndrome can result in improved quality of life for these patients.
Generating Active “L-Pd(0)” via Neutral or Cationic π-Allylpalladium Complexes Featuring Biaryl/Bipyrazolylphosphines: Synthetic, Mechanistic, and Structure–Activity Studies in Challenging Cross-Coupling Reactions (2015)

Two new classes of highly active yet air- and moisture-stable π-R-allylpalladium complexes containing bulky biaryl- and bipyrazolylphosphines with extremely broad ligand scope have been developed. Neutral π-allylpalladium complexes incorporated a range of biaryl/bipyrazolylphosphine ligands, while extremely bulky ligands were accommodated by a cationic scaffold. These complexes are easily activated under mild conditions and are efficient for a wide array of challenging C-C and C-X (X = heteroatom) cross-coupling reactions. Their high activity is correlated to their facile activation to a 12-electron-based "L-Pd(0)" catalyst under commonly employed conditions for cross-coupling reactions, noninhibitory byproduct release upon activation, and suppression of the off-cycle pathway to form dinuclear (μ-allyl)(μ-Cl)Pd2(L)2 species, supported by structural (single crystal X-ray) and kinetic studies. A broad scope of C-C and C-X coupling reactions with low catalyst loadings and short reaction times highlight the versatility and practicality of these catalysts in organic synthesis.
Loss ofALS2Function Is Insufficient to Trigger Motor Neuron Degeneration in Knock-Out Mice But Predisposes Neurons to Oxidative Stress (2005)

Amyotrophic lateral sclerosis (ALS), the most common motor neuron disease, is caused by a selective loss of motor neurons in the CNS. Mutations in the ALS2 gene have been linked to one form of autosomal recessive juvenile onset ALS (ALS2). To investigate the pathogenic mechanisms of ALS2, we generated ALS2 knock-out (ALS2(-/-)) mice. Although ALS2(-/-) mice lacked obvious developmental abnormalities, they exhibited age-dependent deficits in motor coordination and motor learning. Moreover, ALS2(-/-) mice showed a higher anxiety response in the open-field and elevated plus-maze tasks. Although they failed to recapitulate clinical or neuropathological phenotypes consistent with motor neuron disease by 20 months of age, ALS2(-/-) mice or primary cultured neurons derived from these mice were more susceptible to oxidative stress compared with wild-type controls. These observations suggest that loss of ALS2 function is insufficient to cause major motor deficits or motor neuron degeneration in a mouse model but predisposes neurons to oxidative stress.
The regulation of BLyS expression levels through MAPK signal pathway in multiple myeloma (2011)

Objective To investigate the activation of MAPK signal pathway in multiple myeloma and the regulation of BLyS expression levels through MAPK signal pathway; preliminarily study the role of MAPK signal pathway in the up-regulation of BLyS expression levels induced by IFN-γ.Methods Activated MAPK pathway were detected by Western blot,while the expression of BLyS were detected with RT-PCR and Western blot,and Western blot investigated the effect of MAPK pathway on BLyS expression levels induced by IFN-γ.Results In addition to the expression of ERK,JNK,p38,p-JNK was also expressed in MM cell lines,the MAPK pathway inhibitor targeting JNK SP600125 can down-regulate the expression of BLyS,and its activator anisomycin can up-regulate the expression of BLyS.SP600125 restrained the proliferation and survival of MM cells.Conclusion JNK/SAPK pathway was activated in MM cells; The activated degree of JNK/SAPK pathway and the expression level of BLyS was positively correlated.JNK/SAPK pathway play an important role in the up-regulation of BLyS expression levels induced by IFN-γ.

Key words: 
Multiple myeloma;  B-lymphocyte stimulator (BLyS) ;  MAPK signal pathway
Oncogenic FGFR3 gene fusions in bladder cancer (2012)

FGF receptor 3 (FGFR3) is activated by mutation or over-expression in many bladder cancers. Here, we identify an additional mechanism of activation via chromosomal re-arrangement to generate constitutively activated fusion genes. FGFR3-transforming acid coiled coil 3 (TACC3) fusions resulting from 4p16.3 re-arrangements and a t(4;7) that generates a FGFR3-BAI1-associated protein 2-like 1 (BAIAP2L1) fusion were identified in 4 of 43 bladder tumour cell lines and 2 of 32 selected tissue samples including the tumour from which one of the cell lines was derived. These are highly activated and transform NIH-3T3 cells. The FGFR3 component is identical in all cases and lacks the final exon that includes the phospholipase C gamma 1 (PLCγ1) binding site. Expression of the fusions in immortalized normal human urothelial cells (NHUC) induced activation of the mitogen-activated protein kinase pathway but not PLCγ1. A protein with loss of the terminal region alone was not as highly activated as the fusion proteins, indicating that the fusion partners are essential. The TACC3 fusions retain the TACC domain that mediates microtubule binding and the BAIAP2L1 fusion retains the IRSp53/MIM domain (IMD) that mediates actin binding and Rac interaction. As urothelial cell lines with FGFR3 fusions are extremely sensitive to FGFR-selective agents, the presence of a fusion gene may aid in selection of patients for FGFR-targeted therapy.
Methotrexate analogs. 31. Meta and ortho isomers of aminopterin, compounds with a double bond in the side chain, and a novel analog modified at the .alpha.-carbon: chemical and in vitro biological studies (1988)

Five heretofore undescribed analogues of methotrexate (MTX) and aminopterin (AMT) were synthesized and tested as dihydrofolate reductase (DHFR) inhibitors and tumor cell growth inhibitors. The meta isomer of AMT was obtained from 2,4-diamino-6-(bromomethyl)pteridine and m-(aminobenzoyl)-L-glutamic acid, while the ortho isomer was obtained via the same route by using alpha-methyl gamma-tert-butyl o-(aminobenzoyl)-L-glutamate instead of the free acid. Analogues of MTX and AMT containing a double bond in the side chain were prepared from dimethyl D,L-2-amino-4-hexenedioate and 4-amino-4-deoxy-N10-methylpteroic acid and 4-amino-4-deoxy-N10-formylpteroic acid, respectively. Finally, a positional isomer of MTX with the CH2CH2COOH moiety moved from the alpha-carbon to the adjacent carboxamide nitrogen was synthesized from 3-[N-(carboxymethyl)amino]propanoic acid diethyl ester and 4-amino-4-deoxy-N10-methylpteroic acid. The positional isomers of AMT were weak DHFR inhibitors and showed very little growth-inhibitory activity against L1210 murine leukemia cells or the MTX-resistant L1210/R81 mutant line in culture. The MTX and AMT analogues with the CH2CH2COOH moiety replaced by a CH2CH = CHCOOH side chain showed anti-DHFR activity similar to that of the previously described saturated compound N-(4-amino-4-deoxy-N10-methylpteroyl)-L-2-aminoadipic acid, but were less potent than the parent drugs. The MTX analogue with the CH2CH2COOH side chain displaced from C to N was weakly bound to DHFR, confirming the importance of an intact CONH moiety, and showed greatly diminished cell growth inhibitory potency relative to MTX. None of the compounds was a substrate for folylpolyglutamate synthetase (FPGS) from mouse liver. Furthermore, inhibition of folic acid polyglutamylation in vitro at equimolar 500 microM concentrations of drug and substrate was negligible. The structural changes embodied in these five novel compounds are therefore too great for binding to the FPGS active site.
The Human Immunoglobulin Kappa Variable (IGKV) Genes and Joining (IGKJ) Segments (1998)

‘Human Immunoglobulin Kappa Variable (IGKV) Genes and Joining (IGKJ) Segments’, second report of the ‘IMGT Locus on Focus’ section, comprises five tables entitled: (1) ‘Number of human germline IGKV genes at 2p12 and potential repertoire’; (2) ‘Human germline IGKV gene table’; (3) ‘Human IGKV allele table’; (4) ‘Human germline IGKJ table’ and (5) ‘Human IGKJ allele table’. These tables are available at the IMGT Marie-Paule page from &lt;b&gt;IMGT&lt;/b&gt;, the international ImMunoGeneTics database (&lt;b&gt;http://imgt.cnusc.fr:8104&lt;/b&gt;) created by Marie-Paule Lefranc, CNRS, Université Montpellier II, Montpellier, France.