gebhart/patrepeval huggingface dataset:
Deoxyribonucleoside Cyclic 3',5'-Phosphorofluondates (1996)

Abstract The synthesis of nucleoside cyclic 3′,5′-phosphorofluoridates, so far not described compounds in the chemical literature, have been performed. As a key substrate we used 2′-deoxyribonucleoside cyclic 3′,5′-phosphorothioates (1) which have been obtained in this Laboratory several years ago.1
Identification and Characterization of the New Osteoclast Progenitor with Macrophage Phenotypes Being Able to Differentiate into Mature Osteoclasts (2000)

Osteoclasts are thought to belong to a macrophage lineage. However, the nature of common precursors of osteoclasts and macrophages remains to be investigated. We have characterized the differentiation potential of mouse bone marrow macrophages into mature osteoclasts. Monocyte macrophage-colony-stimulating factor (M-CSF) stimulated the proliferation of bone marrow macrophages in a dose-dependent manner and these M-CSF-dependent bone marrow macrophage (MDBM) cells efficiently differentiated into the tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts in the presence of soluble RANKL (sRANKL) and M-CSF in the in vitro culture. The macrophage-like cell line TMC16 was established from tsA58 (temperature-sensitive SV40 large T-antigen) transgenic mice in the same manner to the preparation of MDBM cells and also differentiated into mature osteoclasts. During this differentiation in vitro, the morphology of the cells changed from spindle to round and smaller (termed pOC) on day 2 and to multinuclear (termed multinucleated cells [MNCs]) on day 4. The surface expression of macrophage marker CD14 was down-regulated and that of CD43 was up-regulated on pOC, analyzed by flow cytometry. RNA analysis revealed that osteoclast marker genes such as calcitonin receptor (CTR), carbonic anhydrase II (CAII), cathepsin K (cath K), MMP9, and TRAP were strongly expressed in MNCs and weakly in pOC whereas MDBM cells did not express these genes. However, the osteopontin (OPN) gene was strongly expressed in MDBM cells and this expression became weakened after differentiation into pOC. The TMC16 cell line weakly expressed cath K, TRAP, and OPN, suggesting that the TMC16 cell line is immortalized at a stage slightly differentiated from MDBM cells. Furthermore, cell sorting analysis revealed that osteoclast early progenitors in bone marrow cells are preferentially present in the Mac-1- F4/80dull population, which differentiated into MDBM cells (the osteoclast progenitor) expressing Mac-1+ F4/80int, suggesting that M-CSF plays roles of a differentiation factor as well as a growth factor for osteoclast early progenitors. These results showed the transition of morphology, surface markers, and gene expression from the early to mature stage in osteoclast differentiation. We propose three differentiation stages in the osteoclast lineage: the pro-osteoclast (spindle-shaped macrophage cells), the pre-osteoclast (small round mononucleated TRAP-positive cells), and the mature osteoclast (multinucleated TRAP-positive cells) stage.
The Oxidation of Water-Soluble Organic Fuels Using Platinum-Tin Catalysts (1969)

Electrodeposited platinum‐tin mixtures show enhanced activity toward the oxidation of methanol, formaldehyde, and formic acid when compared with platinum black. This increased activity is particularly noticeable with formaldehyde, the anode polarization being decreased by 0.4V at a current density of 100 mA/cm2.
Immunological Associations in Familial and Non-Familial Alzheimer Patients and Their Families (1994)

A number of autoimmune diseases and immune-related conditions were investigated in a series of 100 Alzheimer patients and their families. The group was divided into those who had familial dementia of the Alzheimer type and non-familial dementia of the Alzheimer type. HLA DR3 was associated with the familial dementia of the Alzheimer type patients. Adult exposure to tuberculosis appeared to be a risk factor for familial dementia of the Alzheimer type patients. Autoimmune diseases clustered among the non-familial dementia of the Alzheimer type patients, and also among their relatives. Asthma and infertility were also significantly increased among non-familial dementia of the Alzheimer type relatives. The analysis showed that (1) autoimmunity may be important in the sporadic form of Alzheimer disease; (2) it may be possible to confer a decreased risk for Alzheimer disease among relatives when many autoimmune diseases occur in the family; (3) it may be important to assess environmental risk factors for Alzheimer disease separately in patients with familial and sporadic disease; and (4) the efficacy of drug therapies may be dependent on whether the patients have a familial or sporadic form of Alzheimer disease.
Structural implications for the design of molecular vaccines. (2000)

The major histocompatibility complex molecules bind and present short antigenic peptide fragments on the surface of antigen presenting cells to T-cell receptors. Recognition of peptide-MHC by cytotoxic T-cells initiates a cascade of signals to T-cells, which in turn destroy the antigen presenting cell. In the design of molecular vaccines for the treatment of diseases, an understanding of the 3-dimensional structure of MHC class I and is interaction with both peptide and T-cell receptor is an important prerequisite. In this review, we will discuss such crystal structures, as well as structures of glycopeptides and alternative T-cell antigens presented by MHC molecules.
Targeted radiosensitisation by pegylated liposome-encapsulated 3′, 5′-O-dipalmitoyl 5-iodo-2′-deoxyuridine in a head and neck cancer xenograft model (2004)

5-Iodo-2'-deoxyuridine (IUdR) is an effective radiosensitiser but its clinical development has been limited by toxicity. Prolonged intravenous infusions of IUdR are necessary for optimal tumour uptake but cause dose-limiting myelosuppression. The lack of selective tumour uptake can lead to radiosensitisation of adjacent normal tissues and enhanced local radiation toxicity. Liposomal IUdR delivery offers selective targeting of tumour tissues and avoidance of local and systemic toxicity. In these studies, we report the development of a pegylated liposome containing a lipophilic IUdR derivative (3', 5'-O-dipalmitoyl-5-iodo-2'-deoxyuridine) for use in a head and neck cancer xenograft model. Initial studies confirmed the ability of IUdR to sensitise two head and neck cancer cell lines to single fractions of radiotherapy (SFRT) and this effect was seen to correlate with the thymidine replacement index in KB cells. In vivo delivery of single doses of either unencapsulated IUdR or pegylated liposomal IUdR (PLIUdR) to nude mice bearing KB xenograft tumours did not enhance the effect of SFRT delivered 16 h later. When PLIUdR was delivered by a protracted administration schedule to a dose of 48 mg kg(-1) over 7 days, it enhanced the effect of both 4.5 Gy SFRT and fractionated radiotherapy. PLIUdR was at least as effective as unencapsulated IUdR delivered by multiple intravenous injections or continuous subcutaneous infusion. Immunohistochemistry with a specific anti-IUdR monoclonal antibody confirmed greater levels of tumour staining in tumours from animals treated with PLIUdR compared with those treated with unencapsulated IUdR.
First General Route to Substituted α-Arylamino-α′-chloropropan-2-ones by Oxidation of N-Protected Aminohalohydrins: The Importance of Disrupting Hydrogen Bond Networks (2010)

The presence of a network of intra- and intermolecular hydrogen bonds in β-arylamino alcohols, confirmed by both IR spectroscopy and computer modeling, inhibits their oxidation to the corresponding α-amino ketones. A straightforward protocol, including highly regioselective protection (as carbamates) and subsequent oxidation with Dess-Martin periodinane, affords near quantitative yields of the desired N-protected ketones, which upon mild treatment with iodotrimethylsilane leads to a series of differently functionalized α-arylamino-α′-chloro ketones.
Managerial and organizational perspectives (2005)

Abstract Organizational and managerial theories may also give support to the understanding of cooperative strategy. This chapter first looks into the strategic management theory (SMT) in which some of the possible motives for establishing alliances can be identified. The chapter explains how the compatibility of goals has to be considered as an important element of selecting partners, and describes how partner systems and cultures should be able to achieve integration. It looks into how the game theory serves as a set of techniques that draw attention to the possible consequences in noncooperative and cooperative behaviour, while also explaining how the Prisoners' Dilemma indicates the behavioural options between partners. It also considers the resource dependency perspective and analyses how alliances are organized and how trust proves to be significant in cooperative endeavours.
Dentofacial features of a family with Crouzon syndrome. Case reports (1997)

Crouzon syndrome is an autosomal dominant condition characterized by craniosynostosis with associated dentofacial anomalies. This paper describes the variable clinical features in affected individuals over two generations of a family with particular reference to the dentofacial deformities and discussion of management strategies.
Building Program Vector Representations for Deep Learning (2014)

Deep learning has made significant breakthroughs in various fields of artificial intelligence. Advantages of deep learning include the ability to capture highly complicated features, weak involvement of human engineering, etc. However, it is still virtually impossible to use deep learning to analyze programs since deep architectures cannot be trained effectively with pure back propagation. In this pioneering paper, we propose the "coding criterion" to build program vector representations, which are the premise of deep learning for program analysis. Our representation learning approach directly makes deep learning a reality in this new field. We evaluate the learned vector representations both qualitatively and quantitatively. We conclude, based on the experiments, the coding criterion is successful in building program representations. To evaluate whether deep learning is beneficial for program analysis, we feed the representations to deep neural networks, and achieve higher accuracy in the program classification task than "shallow" methods, such as logistic regression and the support vector machine. This result confirms the feasibility of deep learning to analyze programs. It also gives primary evidence of its success in this new field. We believe deep learning will become an outstanding technique for program analysis in the near future.
Class modification in the GemStone object-oriented DBMS (1987)

We are currently designing a class modification methodology for GemStone. We describe the current status of the design. We choose from two basic approaches and then introduce those aspects of GemStone necessary for an understanding of the paper. After defining a set of invariants for GemStone databases, we discuss specific class modification operations in terms of maintaining these invariants. We next discuss several issues that impact class modification. These issues include concurrency and authorization, and lead to difficult choices.
Interferometric construction of circular gratings (1980)

Low noise diffraction gratings are constructed with the aid of a circular grating interferometer illuminated with a polychromatic or extended source.
Disorganization of the Golgi complex and the cytoplasmic microtubule system in CHO cells exposed to okadaic acid (1992)

A combination of immunocytochemical and electron microscopic methods was used to study the effects of okadaic acid, a specific inhibitor of protein phosphatase types 1 and 2A, on the Golgi complex and the microtubule system of interphase CHO cells. At a concentration of 0.25 microM and within 2-3 h of exposure, okadaic acid caused a reversible disorganization of the Golgi complex, observed as a disintegration of the stacks of cisternae and formation of clusters of tubules and vesicles dispersed in the cytoplasm. At the same time, staining for mannosidase II was shifted from the Golgi stacks to the endoplasmic reticulum, whereas the clusters of tubules and vesicles for the main part were negative. This change in localization of the enzyme was not blocked by cycloheximide and thus not dependent on ongoing protein synthesis. The changes in the morphology of the Golgi complex were coordinated in time with a remodelling of the microtubule system, observed as a reduction in the number of microtubules, a tendency of the remaining microtubules to arrange in an aster-like pattern, and an increased sensitivity to low concentrations of the microtubule-disruptive drug nocodazole. After removal of the drug, the microtubule system was rapidly normalized (1-2 h) and subsequently also the Golgi complex (4-8 h). The results suggest that okadaic acid induces a redistribution of the Golgi stacks into the endoplasmic reticulum, leaving the trans-most elements behind as tubules and vesicles.(ABSTRACT TRUNCATED AT 250 WORDS)
Properties of Secretin Receptor Internalization Differ from Those of the β2-Adrenergic Receptor (1999)

The endocytic pathway of the secretin receptor, a class II GPCR, is unknown. Some class I G protein-coupled receptors (GPCRs), such as the beta(2)-adrenergic receptor (beta(2)-AR), internalize in clathrin-coated vesicles and this process is mediated by G protein-coupled receptor kinases (GRKs), beta-arrestin, and dynamin. However, other class I GPCRs, for example, the angiotensin II type 1A receptor (AT(1A)R), exhibit different internalization properties than the beta(2)-AR. The secretin receptor, a class II GPCR, is a GRK substrate, suggesting that like the beta(2)-AR, it may internalize via a beta-arrestin and dynamin directed process. In this paper we characterize the internalization of a wild-type and carboxyl-terminal (COOH-terminal) truncated secretin receptor using flow cytometry and fluorescence imaging, and compare the properties of secretin receptor internalization to that of the beta(2)-AR. In HEK 293 cells, sequestration of both the wild-type and COOH-terminal truncated secretin receptors was unaffected by GRK phosphorylation, whereas inhibition of cAMP-dependent protein kinase mediated phosphorylation markedly decreased sequestration. Addition of secretin to cells resulted in a rapid translocation of beta-arrestin to plasma membrane localized receptors; however, secretin receptor internalization was not reduced by expression of dominant negative beta-arrestin. Thus, like the AT(1A)R, secretin receptor internalization is not inhibited by reagents that interfere with clathrin-coated vesicle-mediated internalization and in accordance with these results, we show that secretin and AT(1A) receptors colocalize in endocytic vesicles. This study demonstrates that the ability of secretin receptor to undergo GRK phosphorylation and beta-arrestin binding is not sufficient to facilitate or mediate its internalization. These results suggest that other receptors may undergo endocytosis by mechanisms used by the secretin and AT(1A) receptors and that kinases other than GRKs may play a greater role in GPCR endocytosis than previously appreciated.
Lysis-filtration blood culture versus conventional blood culture in a bacteremic rabbit model (1982)

Thirteen representative pathogenic bacterial species were used to create septicemia in rabbits, by injecting 10(6) colony-forming units into the marginal ear vein. At a selected time, usually 30 to 60 min after injection, heart blood was drawn into heparin and dispensed in 5.0-,0.5-, and 0.1-ml volumes into duplicate bottles of commercial brain heart infusion broth with sodium polyanetholesulfonate, and into duplicate bottles of a newly developed blood-lysing solution. Lysed blood was filtered, and the filter membranes were cultured in brain heart infusion broth. At the 5.0-ml blood inoculum level, of 126 total culture bottles (63 rabbits) for each system, 83 conventional cultures versus 109 lysis-filtration cultures were positive. At the 0.5-ml blood inoculum, 20 of 126 conventional culture bottles were positive, versus 66 of 126 lysis-filtration cultures. At the 0.1-ml blood inoculum, 2 of 126 conventional culture bottles were positive, versus 30 of 126 lysis-filtration cultures. Overall, 105 of 378 conventional cultures and 205 of 378 lysis-filtration cultures were positive. The advantage of the lysis-filtration system was striking for both gram-positive and gram-negative organisms at all inoculum concentrations, but was greater for gram-positive organisms. Most significant was the rate of recovery by this new system, when the number of bacteria in the blood was reduced to the point where recovery by conventional culture was unlikely. It is postulated that the superiority of lysis-filtration culture may be due to release of bacteria by lysis of phagocytes, preventing continued loss of pathogens by intracellular destruction during the first hours of blood culture.
Non‐solid oncogenes in solid tumors: EML4–ALK fusion genes in lung cancer (2008)

It is generally accepted that recurrent chromosome translocations play a major role in the molecular pathogenesis of hematological malignancies but not of solid tumors. However, chromosome translocations involving the e26 transformation-specific sequence transcription factor loci have been demonstrated recently in many prostate cancer cases. Furthermore, through a functional screening with retroviral cDNA expression libraries, we have discovered the fusion-type protein tyrosine kinase echinoderm microtubule-associated protein like-4 (EML4)-anaplastic lymphoma kinase (ALK) in non-small cell lung cancer (NSCLC) specimens. A recurrent chromosome translocation, inv(2)(p21p23), in NSCLC generates fused mRNA encoding the amino-terminal half of EML4 ligated to the intracellular region of the receptor-type protein tyrosine kinase ALK. EML4-ALK oligomerizes constitutively in cells through the coiled coil domain within the EML4 region, and becomes activated to exert a marked oncogenicity both in vitro and in vivo. Break and fusion points within the EML4 locus may diverge in NSCLC cells to generate various isoforms of EML4-ALK, which may constitute approximately 5% of NSCLC cases, at least in the Asian ethnic group. In the present review I summarize how detection of EML4-ALK cDNA may become a sensitive diagnostic means for NSCLC cases that are positive for the fusion gene, and discuss whether suppression of ALK enzymatic activity could be an effective treatment strategy against this intractable disorder.
Structure and organization of the hepatitis C virus genome isolated from human carriers (1991)

Hepatitis C virus (HCV) is a major causative agent of posttransfusion non-A, non-B hepatitis, which often develops into malignant chronic diseases, including liver cirrhosis and hepatocellular carcinoma. We have cloned from human carriers overlapping cDNAs (9,416 bp) covering the entire coding region of the HCV genome. The latter encodes a 3,010-amino-acid polyprotein. In addition, there are 332 and 54 bases of 5' and 3' noncoding sequences, respectively. Our HCV strain has a 77% nucleic acid identity to the HCV strain cloned by workers at Chiron Corporation. The hydrophobicity profile of the putative polyprotein is similar to those of flaviviruses, but it has limited amino acid homology to polyproteins of flaviviruses and other viruses, indicating that HCV is at most distantly related to flaviviruses.
Design, Synthesis, and Biological Evaluation of Indolequinone Phosphoramidate Prodrugs Targeted to DT-diaphorase (2002)

A series of 2- and 3-substituted indolequinone phosphoramidate prodrugs targeted to DT-diaphorase (DTD) have been synthesized and evaluated. These compounds are designed to undergo activation via quinone reduction by DTD followed by expulsion of the phosphoramide mustard substituent from the hydroquinone. Chemical reduction of the phosphoramidate prodrugs led to rapid expulsion of the corresponding phosphoramidate anions in both series of compounds. Compounds substituted at the 2-position are excellent substrates for human DTD (k(cat)/K(M) = (2-5) x 10(6) M(-1) s(-1)); however, compounds substituted at the 3-position are potent inhibitors of the target enzyme. Both series of compounds are toxic in HT-29 and BE human colon cancer cell lines in a clonogenic assay. There was a correlation found between cytotoxicity and DTD activity for the 2-series of phosphoramidates; however, there was no correlation between cytotoxicity and DTD activity in the 3-series of compounds. This finding suggests the presence of an alternative mechanism for the activation of these compounds.
Genetic Ablation of Metadherin Inhibits Autochthonous Prostate Cancer Progression and Metastasis (2014)

Metadherin (MTDH) overexpression in diverse cancer types has been linked to poor clinical outcomes, but definitive genetic proof of its contributions to cancer remains incomplete. In particular, the degree to which MTDH may contribute to malignant progression in vivo is lacking. Here, we report that MTDH is amplified frequently in human prostate cancers where its expression levels are tightly correlated with prostate cancer progression and poor disease-free survival. Furthermore, we show that genetic ablation of MTDH in the transgenic adenomcarcinoma of mouse prostate (TRAMP) transgenic mouse model of prostate cancer blocks malignant progression without causing defects in the normal development of the prostate. Germline deletion of Mtdh in TRAMP mice prolonged tumor latency, reduced tumor burden, arrested progression of prostate cancer at well-differentiated stages, and inhibited systemic metastasis to distant organs, thereby decreasing cancer-related mortality ∼10-fold. Consistent with these findings, direct silencing of Mtdh in prostate cancer cells decreased proliferation in vitro and tumor growth in vivo, supporting an epithelial cell-intrinsic role of MTDH in prostate cancer. Together, our findings establish a pivotal role for MTDH in prostate cancer progression and metastasis and define MTDH as a therapeutic target in this setting. Cancer Res; 74(18); 5336-47. ©2014 AACR.
CTACK, a skin-associated chemokine that preferentially attracts skin-homing memory T cells (1999)

In contrast to naive lymphocytes, memory/effector lymphocytes can access nonlymphoid effector sites and display restricted, often tissue-selective, migration behavior. The cutaneous lymphocyte-associated antigen (CLA) defines a subset of circulating memory T cells that selectively localize in cutaneous sites mediated in part by the interaction of CLA with its vascular ligand E-selectin. Here, we report the identification and characterization of a CC chemokine, cutaneous T cell-attracting chemokine (CTACK). Both human and mouse CTACK are detected only in skin by Southern and Northern blot analyses. Specifically, CTACK message is found in the mouse epidermis and in human keratinocytes, and anti-CTACK mAbs predominantly stain the epithelium. Finally, CTACK selectively attracts CLA(+) memory T cells. Taken together, these results suggest an important role for CTACK in recruitment of CLA(+) T cells to cutaneous sites. CTACK is predominantly expressed in the skin and selectively attracts a tissue-specific subpopulation of memory lymphocytes.